https://ringo.ams.stonybrook.edu/api.php?action=feedcontributions&user=Lprentis&feedformat=atomRizzo_Lab - User contributions [en]2020-10-01T02:31:55ZUser contributionsMediaWiki 1.29.0https://ringo.ams.stonybrook.edu/index.php?title=Tutorials&diff=13466Tutorials2020-09-15T15:28:29Z<p>Lprentis: </p>
<hr />
<div>{| cellpadding=0 width=90%<br />
*[[DOCK_VS Tutorials]] - Traditional Virtual Screening<br />
*[[DOCK_DN Tutorials]] - De Novo Design<br />
<!-- *[[DOCK_GA Tutorials]] - Genetic Algorithm --><br />
*[[DOCK_CV Tutorials]] - Covalent Docking <br />
*[[DOCK_GA Tutorials]] - Genetic Algorithm<br />
*[[Ligand Enrichment Tutorial]] - Ligand Enrichment Tutorial<br />
|}<br />
<br />
Disclaimer: The tutorials are written by students learning to use dock in a classroom setting. A new dock tutorial is created every year collaboratively by students in the AMS 536 class. All the tutorials follow a similar progression, but are built around different protein-ligand complexes from the PDB.<br />
<br />
Some of the input files may have been modified to reduce runtime in order to work well in a classroom setting. For production work, please consult the current DOCK Manual for details.</div>Lprentishttps://ringo.ams.stonybrook.edu/index.php?title=Rizzo_Lab_Information_and_Tutorials&diff=13465Rizzo Lab Information and Tutorials2020-09-15T15:27:05Z<p>Lprentis: /* DOCK */</p>
<hr />
<div>== DOCK ==<br />
{| cellpadding=0 width=90%<br />
*[http://dock.compbio.ucsf.edu/DOCK_6/dock6_manual.htm Online Users Manual]<br />
*[[Tutorials]]<br />
*[[Benchmarking]]<br />
*[[Developer's Info]]<br />
*[[Testset Protocols]]<br />
*[[Parameter List/Explanations]]<br />
*[[Scoring Functions]]<br />
*[[Example Input Files]]<br />
*[[DOCK Abbreviations Guide]]<br />
*[[Advanced Dock Utilities/Information]]<br />
*[[DOCK6 POSE Reproduction]]<br />
|}<br />
<br />
== Visualization Software ==<br />
*[[Chimera]]<br />
*[[MOE]]<br />
*[[VMD]]<br />
<br />
== Basic Linux Tools==<br />
{| cellpadding=0 width=90%<br />
*[[Unix]]<br />
*[[vi ]]<br />
*[[sed - Stream Editor in Unix]]<br />
*[[Slick awk tricks]]<br />
*[[Ways to remove the first line]]<br />
*[[PBS Queue]]<br />
*[[gdb (GNU Debugger)]]<br />
*[[Common Errors - ctrl M]]<br />
*[[C Shell Scripting]]<br />
*[[Unix find]]<br />
*[[Which Unix Distribution?]]<br />
*[[rsync]]<br />
*[[MPICH]]<br />
*[[Secure Shell (ssh)]]<br />
*[[Archiving old data]]<br />
*[[valgrind]]<br />
*[[Ghostscript]]<br />
|}<br />
<br />
== Molecular Dynamics ==<br />
{| cellpadding=0 width=90%<br />
*[[AMBER Tutorials]]<br />
*[[AMBER TI Tutorials]]<br />
*[[AMBER Lipid Tutorials]]<br />
*[[AMBER tricks]]<br />
*[[NAMD tutorial]]<br />
*[[NAMD Amber inputs]]<br />
*[[per-residue energy decompositions]]<br />
*[[nonstandard residues prep]]<br />
*[[ptraj]]<br />
*[[Blocked Standard Error of the Mean]]<br />
|}<br />
<br />
== GROMACS ==<br />
{| cellpadding=0 width=90%<br />
* [[Compiling GROMACS on Cluster]]<br />
* [[MD Simulation: Protein in Water]]<br />
|}<br />
<br />
== Monte Carlo ==<br />
*[[BOSS Pure Liquid Simulation Notes]]<br />
<br />
== Analysis Tools ==<br />
* [[Analysis Tools Repository]]<br />
* [[MATLAB]]<br />
* [[Octave]]<br />
* [[R - Statistical Computing]]<br />
* [[gnuplot]]<br />
* [[pylab]]<br />
<br />
== Databases ==<br />
*[http://pubchem.ncbi.nlm.nih.gov/ PubChem (ligand database)]<br />
*[http://webbook.nist.gov/chemistry/ NIST (small molecule database)]<br />
*[[ZINC12 Database]]<br />
*[[ZINC15 Database]]<br />
*[[Families in the Protein Databank]]<br />
*[[Automated Family generation from PDB]]<br />
*[[Drug-like organic molecules]]<br />
<br />
== Conversion between file types ==<br />
* [[Amber to pdb]]<br />
* [[Amber to mol2 (protein)]]<br />
* [[NAMD to mol2 ]]<br />
* [[pdb to mol2]]<br />
* [[SDF to mol2]]<br />
<br />
== Setting up accounts ==<br />
{| cellpadding=0 width=90%<br />
*[[Activating your Seawulf Account]]<br />
*[[Rotation students Wiki]]<br />
|}<br />
<br />
== AutoDock4 ==<br />
{|<br />
*[[AutoDock4 Pose Reproduction Tutorial]]<br />
*[[AutoDock4 Crossdock]]<br />
*[[AutoDock4 Benchmark Results]]<br />
|}<br />
<br />
== AutoDock Vina ==<br />
{|<br />
*[[AutoDock Vina Pose Reproduction Tutorial]]<br />
*[[AutoDock Vina Benchmark Results]]<br />
|}<br />
<br />
== Miscellaneous ==<br />
{| cellpadding=0 width=90%<br />
* [[How to write Makefiles]]<br />
* [[X-Win32]] <br />
* [[CVS Commands]]<br />
* [[Ethernet Cables]]<br />
* [[Sequence alignment]] <br />
* [[Making images for publication]]<br />
* [[Lab-designed code and programs]]<br />
* [[Server Administration]]<br />
* [[Amber on Seawulf (compilation)]]<br />
* [[Cluster compilations]]<br />
* [[NAMD on Seawulf]]<br />
* [[Semester Checklist]]<br />
* [[Wiki Editing]]<br />
*[[Other Meetings]]<br />
*[[Seawulf Cluster Assessment]]<br />
*[[Formatting your Thesis]]<br />
*[[Setting up insurance through Research Foundation]]<br />
|}<br />
<br />
==Archive==<br />
*[[Legacy Info]]</div>Lprentishttps://ringo.ams.stonybrook.edu/index.php?title=DOCK_Release_Objectives&diff=13464DOCK Release Objectives2020-09-15T15:21:15Z<p>Lprentis: </p>
<hr />
<div>DOCK 6.10 To do list<br />
<br />
*(1)Update the FMS and FPS test cases<br />
<br />
*(2)Change variables in the FMS and FPS<br />
<br />
*(3)Merge all the changes with the latest CVS version for testing<br />
<br />
*(4)Update the DOCK 6.9 HTM file<br />
<br />
*(5)Perform the descriptor tests<br />
<br />
*(6)Check in the changes to DOCK CVS Tree<br />
<br />
Developer To Do:<br />
# <s>Test Courtney's orienting fixx</s><br />
# <s>Test Brian's rotatable bond fix</s><br />
# <s>HMS = NA vs 9999 and implications on dn generic</s><br />
# HMS pruning in database filter<br />
# database filter to charge molecule with gasteiger charge<br />
# score molecule = no, internal energy = yes problem<br />
<br />
POTENTIAL DOCK DESCRIPTORS<br />
# QED<br />
# logp<br />
# logS<br />
# aromatic rings<br />
# lipinski alerts/violations<br />
# ligand SASA<br />
# ligand desolvation penalty<br />
# polar surface area<br />
# Rizzo coefficient<br />
#</div>Lprentishttps://ringo.ams.stonybrook.edu/index.php?title=DOCK_Release_Objectives&diff=13463DOCK Release Objectives2020-09-15T15:16:21Z<p>Lprentis: </p>
<hr />
<div>DOCK 6.10 To do list<br />
<br />
*(1)Update the FMS and FPS test cases<br />
<br />
*(2)Change variables in the FMS and FPS<br />
<br />
*(3)Merge all the changes with the latest CVS version for testing<br />
<br />
*(4)Update the DOCK 6.9 HTM file<br />
<br />
*(5)Perform the descriptor tests<br />
<br />
*(6)Check in the changes to DOCK CVS Tree<br />
<br />
Developer To Do:<br />
# <s>Test Courtney's orienting fixx</s><br />
# <s>Test Brian's rotatable bond fix</s><br />
# <s>HMS = NA vs 9999 and implications on dn generic</s><br />
# database filter to charge molecule with gasteiger charge<br />
# score molecule = no, internal energy = yes problem<br />
<br />
POTENTIAL DOCK DESCRIPTORS<br />
# QED<br />
# logp<br />
# logS<br />
# aromatic rings<br />
# lipinski alerts/violations<br />
# ligand SASA<br />
# ligand desolvation penalty<br />
# polar surface area<br />
# Rizzo coefficient<br />
#</div>Lprentishttps://ringo.ams.stonybrook.edu/index.php?title=DOCK_DN_Development_Goals&diff=13178DOCK DN Development Goals2020-07-20T20:13:15Z<p>Lprentis: /* Current Coding Progress: */</p>
<hr />
<div>This is the Rizzo lab wiki page for coordinating bugs and progress on the de novo project.<br />
<br><br />
<br />
=== Valgrind clean version of the code on cluster that Rizzo lab should be using: ===<br />
Lauren:<br />
/gpfs/projects/rizzo/zzz.programs/dock6.9_release<br />
This version includes all changes of the merge.<br />
<br />
Path to Generic Fragment Library:<br />
/gpfs/projects/rizzo/leprentis/gen-frags-12<br />
<br />
Path to Frequency Anchors:<br />
/gpfs/projects/rizzo/leprentis/zinc1_ancs_freq<br />
<br><br />
<br />
=== Current Coding Progress: ===<br />
Working on these currently:<br />
<br />
# John: Implement fragment frequency picking as an option<br />
# John: Professional web page<br />
# Chris: Guided FPS <br />
# Lauren: Covalent anchor for denovo growth<br />
# Guilherme: rdkit implementation for logp etc<br />
<br />
<br />
<br />
<br><br />
<br />
Need to be fixed/added:<br />
# add print out anchor with frequency option into fraglib code<br />
# MPI option for each anchor <br />
# aromatic rings<br />
# QED<br />
# fraglib generation chirality issue<br />
# chiral centers <br />
# score_molecules and internal_energy problem (for simple_build)<br />
# HMS needs to fixed when no heavy atoms matching<br />
<br />
<br><br />
<br />
Not working on these right now:<br />
# Addition of "3mer" combination fragment check (post tors check)<br />
# Implement Adjacency Matrix into fraglib/dn (initialize matrix and utilize matrix for graph and random fragment picking)<br />
# Min and Max formal charge to replace absolute value of charge.(Broke everything) Step down as layers of growth proceed (layers 1-3 FC = 4, Layers 4-5 FC = 3, Layers 6-8 FC = 2)<br />
# Capping groups for post growth process (halogens and methyls)<br />
# Incorporate tan pruning as final step (post growth) as user option (replace make_unique script) as database filter not dn<br />
<br />
<br><br />
Completed:<br />
# <strike>Lauren: hbond accept/donor descriptor implementation</strike><br />
# <strike>Chris: increase orienting verbose statistics for dn</strike><br />
# <strike>John: acceptance based on freq of torsenv</strike><br />
# <strike>Lauren&John: secondary torenv check of prune dump molecules and testing</strike><br />
# <strike>Lauren&John: SMILEs and ZINC script (for dn and ga)</strike><br />
# <strike>Lauren: add dn name with date and counter function</strike><br />
# <strike>Lauren: Check MGS+(-50)TAN before and after fingerprinting fix for 663 systems</strike><br />
# <strike>Lauren: determine if random seed is reset for each aps</strike><br />
# <strike>Lauren: Create testset for each dn function </strike><br />
# <strike>Lauren: Test simple build function with merged de novo </strike><br />
# <strike>Lauren&Stephen: clean make_unique script for release</strike><br />
# <strike>Lauren: merge GA into dock/dn </strike><br />
# <strike>Dwight & Lauren: MPI wrapper for 192 processors (8 nodes) for testsets on rizzo cluster </strike><br />
# <strike>Lauren: Create short testsets for denovo frag gen, focused fragment generic for DOCK6.9 release </strike><br />
# <strike>Dwight+Lauren: merge parameter files of de novo with DOCK </strike><br />
# <strike>Lauren: add dn_defn file for separate defn with Hydrogens </strike><br />
# <strike>Lauren: Implement csingleton fix for orienting fragments with less than 3 heavy atoms </strike><br />
# <strike>Lauren: Test bfochtman fix for rotatable bonds within an user defined anchor </strike><br />
# <strike>Lauren: Test csingleton fix for orienting fragments with Du </strike><br />
# <strike>Lauren: Test MGS focused fragment library results with dn paper </strike><br />
# <strike>Stephen: editting script to calculate SMILE string of de novo molecules in OpenBabel </strike><br />
# <strike> Stephen: smooth function cutoff for mw </strike><br />
# <strike> Lauren&John: Rework VS protocol to integrate de novo protocol more smoothly </strike><br />
# <strike> Lauren&John: Fix torsion problem for prune_dump molecules </strike><br />
<br><br />
<br />
=== List of features that we definitely want for the 6.9 release: ===<br />
<br />
{| border="1" cellpadding="8" cellspacing="0" style="background:white; text-align:left; width:90%"<br />
|- style="background:lightblue"<br />
! style="width:75%" !|Task<br />
! style="width:15%" !|Owner<br />
! style="width:10%" !|Complete?<br />
|-<br />
|When minimizing with descriptor score, make sure fingerprint is turned off || xxx ||<br />
|-<br />
|Speed up fingerprint calculations by saving reference ligand as a permanent object || WJA || yep<br />
|-<br />
|Add pre-min conformations to growth trees || WJA || yep<br />
|-<br />
|Add verbose flag options || WJA || yep<br />
|-<br />
|Put molecular properties (RB, MW, etc) in mol2 header || WJA || yep<br />
|-<br />
|Put ensemble properties (RB, MW, etc) output stream at the end of each layer || WJA || yep<br />
|-<br />
|Check formal charge prune || BCF || yep<br />
|-<br />
|Combination of horizontal pruning metrics (let's consider dropping tanimoto prune and just using hungarian prune) || WJA || yep<br />
|-<br />
|Finish implementing growth trees || WJA || yep<br />
|-<br />
|Revisit orienting to make sure it is working as intended || WJA || yep<br />
|-<br />
|Fixed a bug where we were marking scaffold_this_layer as true for any fragment || WJA || yep<br />
|-<br />
|Update random sampling function to use last layer changes in graph function || WJA || yep<br />
|-<br />
|Do that same thing for the exhaustive function || WJA || yep<br />
|-<br />
|I don't think we ever clear the scaf_link_sid vector, we definitely should do that somewhere || WJA || yep<br />
|-<br />
|Update exhaustive to combine all frags into one library, just like graph / random. || WJA || yep<br />
|-<br />
|}<br />
<br><br />
<br />
=== List of features/ideas for future releases: ===<br />
<br />
* Using different references for different layers of dn growth (GFPS protocol) Guided footprint similarity - divide the reference into smaller pieces (layers) to help guide the growth paths more efficiently (i.e. directed growth)<br />
* Stereo centers / volume overlap pruning<br />
* Capping group functions (H, CH3, Halogen)<br />
* Incorporate GA at the end of each layer (not easy)<br />
* Overhaul the simple-build function<br />
* Monte carlo algorithm that checks bond frequency<br />
* Scaling max root / layer size with layer<br />
* Select torenv before selecting fragment. Will need to overhaul fraggraph, will keep us from needing to assemble mols that will not pass torenv.<br />
* Add fragname string to restart and dump files, already done for final and fraglib files.<br />
* Add ZINC name to torenv table<br />
* Unusual behavior during library generation when frequency cutoff == 0<br />
* Print out how many molecules cannot be capped. (Difference between ensemble size and dump.)<br />
* building from anchor 0 -> building from scf.98<br />
* Possible torenv check for dump molecules after capping before printing.<br />
* keep tables of what fragments (and torsion types) are already included in a growing molecule (i.e.e the name string has this info) and only accept a new fragment (or torsion type) within certain ranges and probabilities. In other words use knowledge of chemical makeup probabilities to keep from over including or under including certain fragment and bond types (essentially use datamining to help us only build molecules within certain boundaries)<br />
*De novo design with scaled VDW parameters. Exaggerate them and ramp them down or vice versus. May help to eliminate the anchor and slop or anchor and slosh problem.<br />
<br><br />
<br />
=== List of SB2012 systems that we will use for tests: ===<br />
<br />
For now, let's use 5-15 rotatable bonds inclusive; total = 709 systems ("drug-like" size molecules). De novo paper only used 663 systems that removed 46 systems where the cognate ligand did not fall with a +/-2 formal charge. (5through15 = 709, 5through15_ch2 = 663)<br />
<br />
{5RB = 107; 6RB = 96; 7RB = 103; 8RB = 75; 9RB = 66; 10RB = 75; 11RB = 57; 12RB = 41; 13RB = 38; 14RB = 26; 15RB = 25}<br />
<br />
<br></div>Lprentishttps://ringo.ams.stonybrook.edu/index.php?title=Rizzo_Lab_Members_and_Contact_Information&diff=13176Rizzo Lab Members and Contact Information2020-07-20T20:04:58Z<p>Lprentis: /* CURRENT MEMBERS */</p>
<hr />
<div>== CONTACT ==<br />
{| border="1" cellpadding="8" cellspacing="0" style="background:white; text-align:left; width:90%"<br />
|- style="background:white"<br />
! style="width:45%" |Robert C. Rizzo<br />
<br />
Stony Brook University <br />
<br />
Department of Applied Mathematics and Statistics<br />
<br />
Office: Math Tower 1-111<br />
<br />
Lab: Math Tower 3-129<br />
<br />
Stony Brook, NY 11794-3600<br />
<br />
! style="width:45%" |Email: rizzorc [at] gmail [dot] com<br />
<br />
Office: (631) 632-9340<br />
<br />
Lab: (631) 632-8519<br />
<br />
Fax: (631) 632-8490<br />
<br />
Website: rizzolab.org<br />
<br />
Wiki: ringo.ams.sunysb.edu<br />
<br />
|}<br />
<br />
[[Image: Rizzo_lab_2019.png|thumb|center|4000px|'''Current 2019 Rizzo Lab Members:''' ''from left to right'' Stephen, Guilherme, Rodger, Rob, Chris, John, Scott, and Lauren]]<br />
<br />
== CURRENT MEMBERS ==<br />
{| border="1" cellpadding="8" cellspacing="0" style="background:white; text-align:left; width:90%"<br />
|- style="background:lightblue"<br />
! style="width:30%" !|Name<br />
! style="width:20%" !|E-mail<br />
! style="width:10%" !|Status<br />
! style="width:20%" !|Project<br />
! style="width:10%" !|Year<br />
|-<br />
|[http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/people/rizzo.html Dr. Robert C. Rizzo]<br />
||rizzorc [at] gmail [dot] com<br />
||Principal investigator<br />
||Group leader<br />
||2004 - present<br />
|-<br />
|[https://www.gduarter.com Guilherme Duarte Ramos Matos]<br />
||Guilherme.duarteramosmatos [at] stonybrook [dot] edu<br />
||Postdoctoral Researcher<br />
||Cheminformatics integration, COVID-19<br />
||2019 - present<br />
|-<br />
|[http://ringo.ams.sunysb.edu/~lprentis/ Lauren Prentis]<br />
||lauren.prentis [at] stonybrook [dot] edu<br />
||Doctoral Student<br />
||Tsg101, de novo design, covalent docking, genetic algorithm<br />
||2016 - present<br />
|-<br />
|Stephen Telehany<br />
||stephen.telehany [at] stonybrook [dot] edu<br />
||Doctoral Student<br />
||Zika Virus<br />
||2017 - present<br />
|-<br />
|John Bickel<br />
||john.bickel [at] stonybrook [dot] edu<br />
||Doctoral Student<br />
||de novo design, COVID-19<br />
||2019 - present<br />
|-<br />
||Christopher Corbo<br />
||christopher.corbo [at] stonybrook [dot] edu<br />
||Doctoral Student<br />
||Test Set benchmarking, COVID-19<br />
||2019 - present<br />
|-<br />
||Steven Pak<br />
||steven.pak [at] stonybrook [dot] edu<br />
||Doctoral Student<br />
||de novo design, FGFR2, <br />
||2020 - present<br />
|-<br />
||Rodger Tan<br />
||rodger.tan [at] stonybrook [dot] edu<br />
||Undergraduate Student<br />
||Test Set, benchmarking, de novo design<br />
||2019 - present<br />
|-<br />
|Scott Laverty<br />
|scott.laverty [at] stonybrook [dot] edu<br />
|Undergraduate Student<br />
|DOCK6 benchmarking with Autodock4<br />
|2019 - present<br />
|}<br />
<br />
== FORMER MEMBERS ==<br />
{| border="1" cellpadding="8" cellspacing="0" style="background:white; text-align:left; width:90%"<br />
|- style="background:lightgreen"<br />
! style="width 20%" !|Name<br />
! style="width:20%" !|Status<br />
! style="width:20%" !|Project<br />
! style="width:10%" !|Year<br />
! style="width:20%" !|New Position<br />
|-<br />
|Yuchen Zhou<br />
||Doctoral / Masters student<br />
||BoNT/E, DOCK scoring functions, FABP5<br />
||2012 - 2018<br />
|| Postdoc, [http://filizolalab.org/ Filizola Lab] at [https://icahn.mssm.edu/ ISMMS]<br />
|-<br />
|Jiaye Guo<br />
||Doctoral student<br />
||Solvated footprints, Small-molecule inhibitor for HER2<br />
||2013 - 2018<br />
|| Postdoc, [http://www.choderalab.org/ Chodera Lab] at [https://www.mskcc.org/ MSKCC]<br />
|-<br />
|Courtney Singleton<br />
||MD / PhD Student<br />
||HIVgp41, De novo design, genetic algorithm<br />
||2014 - 2018<br />
||Stony Brook Medical School<br />
|-<br />
|Dwight McGee<br />
||Postdoctoral Researcher<br />
||HIVgp41, Free energy calculations, de novo design<br />
||2015 - 2018<br />
|| [http://www.silicontx.com/ Silicon Therapeutics]<br />
|-<br />
|Brian Fochtman<br />
||Doctoral student<br />
||HIVgp41, DOCK development<br />
||2011 - 2017<br />
||The FDA<br />
|-<br />
|Lingling Jiang<br />
||jianglilian68 [at] gmail [dot] com<br />
||HIVgp41, Pharmacophore modeling<br />
||2010 - 2015<br />
||Novo Nordisk<br />
|-<br />
|Brian Ralph<br />
||Undergraduate student<br />
||Fatty acid binding protein, De novo design<br />
||2013 - 2015<br />
||Dental school<br />
|-<br />
|William J. Allen<br />
||Postdoctoral fellow<br />
||HIVgp41, DOCK development<br />
||2011 - 2015<br />
||[http://www.tacc.utexas.edu/ TACC]<br />
|-<br />
|Yulin Huang<br />
||Doctoral student<br />
||EGFR, IGF-IR<br />
||2008 - 2013<br />
||Wall Street<br />
|-<br />
|Sudipto Mukherjee<br />
||Doctoral / Masters student<br />
||DOCK development, HIVgp41<br />
||2005 - 2012<br />
||Postdoc, [http://www.voelzlab.org/ Voelz Lab]<br />
|-<br />
|[http://docking.org/~tbalius/ Trent E. Balius]<br />
||Doctoral student<br />
||EGFR, HIVgp41, DOCK development<br />
||2007 - 2012<br />
||Project Lead, RAS Computational Chemistry Team in the Cancer Research Tecnhology Program (CRTP) at the [https://frederick.cancer.gov/ Frederick National Lab for Cancer Research]<br />
|-<br />
|Patrick Holden<br />
||patrick.m.holden [at] gmail [dot] com<br />
||HIVgp41<br />
||2009 - 2011<br />
|| --<br />
|-<br />
| Jibril Ashiru-Balogun<br />
||Undergraduate student<br />
||HIVgp41<br />
||2010 - 2011<br />
|| --<br />
|-<br />
| Brian Shea<br />
||Undergraduate student<br />
||Kinases <br />
||2010<br />
|| --<br />
|-<br />
| Patrick Murphy<br />
||Undergraduate student<br />
||Influenza <br />
||2009 - 2010<br />
|| --<br />
|-<br />
| Rashi Goyal<br />
||Masters student<br />
||Influenza, HIV <br />
||2007 - 2010<br />
|| --<br />
|-<br />
| Brian McGillick<br />
||Masters student<br />
||HIVgp41<br />
||2007 - 2010<br />
|| --<br />
|-<br />
| Kenneth Ascher<br />
||Undergraduate student<br />
||DOCK method development<br />
||2009 - 2010<br />
|| --<br />
|-<br />
| Dimir Abrar<br />
||Undergraduate student<br />
||HIVRT crossdocking<br />
||2008 - 2009<br />
|| --<br />
|-<br />
| Chetan Raj Rupakheti<br />
||Summer student<br />
||HIVgp41<br />
||2008<br />
|| --<br />
|-<br />
| Bentley Strockbine<br />
||Postdoc <br />
||HIVgp41 <br />
||2005 - 2007<br />
|| --<br />
|-<br />
| Noel Carrascal<br />
||Doctoral student<br />
||DOCK method development<br />
||2005 - 2007<br />
|| --<br />
|-<br />
| Ricky Chachra<br />
||Undergraduate student<br />
||Influenza drug resistance<br />
||2005 - 2007<br />
|| -- <br />
|-<br />
| Amee Patel<br />
||Undergraduate student<br />
||Testset development<br />
||2005 - 2007<br />
|| --<br />
|-<br />
|- <br />
|}</div>Lprentishttps://ringo.ams.stonybrook.edu/index.php?title=Rizzo_Lab_Members_and_Contact_Information&diff=13175Rizzo Lab Members and Contact Information2020-07-20T20:03:58Z<p>Lprentis: /* CONTACT */</p>
<hr />
<div>== CONTACT ==<br />
{| border="1" cellpadding="8" cellspacing="0" style="background:white; text-align:left; width:90%"<br />
|- style="background:white"<br />
! style="width:45%" |Robert C. Rizzo<br />
<br />
Stony Brook University <br />
<br />
Department of Applied Mathematics and Statistics<br />
<br />
Office: Math Tower 1-111<br />
<br />
Lab: Math Tower 3-129<br />
<br />
Stony Brook, NY 11794-3600<br />
<br />
! style="width:45%" |Email: rizzorc [at] gmail [dot] com<br />
<br />
Office: (631) 632-9340<br />
<br />
Lab: (631) 632-8519<br />
<br />
Fax: (631) 632-8490<br />
<br />
Website: rizzolab.org<br />
<br />
Wiki: ringo.ams.sunysb.edu<br />
<br />
|}<br />
<br />
[[Image: Rizzo_lab_2019.png|thumb|center|4000px|'''Current 2019 Rizzo Lab Members:''' ''from left to right'' Stephen, Guilherme, Rodger, Rob, Chris, John, Scott, and Lauren]]<br />
<br />
== CURRENT MEMBERS ==<br />
{| border="1" cellpadding="8" cellspacing="0" style="background:white; text-align:left; width:90%"<br />
|- style="background:lightblue"<br />
! style="width:30%" !|Name<br />
! style="width:20%" !|E-mail<br />
! style="width:10%" !|Status<br />
! style="width:20%" !|Project<br />
! style="width:10%" !|Year<br />
|-<br />
|[http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/people/rizzo.html Dr. Robert C. Rizzo]<br />
||rizzorc [at] gmail [dot] com<br />
||Principal investigator<br />
||Group leader<br />
||2004 - present<br />
|-<br />
|[https://www.gduarter.com Guilherme Duarte Ramos Matos]<br />
||Guilherme.duarteramosmatos [at] stonybrook [dot] edu<br />
||Postdoctoral Researcher<br />
||Cheminformatics integration, COVID-19<br />
||2019 - present<br />
|-<br />
|[http://ringo.ams.sunysb.edu/~lprentis/ Lauren Prentis]<br />
||lauren.prentis [at] stonybrook [dot] edu<br />
||Doctoral Student<br />
||Tsg101, de novo design, covalent docking, genetic algorithm<br />
||2016 - present<br />
|-<br />
|Stephen Telehany<br />
||stephen.telehany [at] stonybrook [dot] edu<br />
||Doctoral Student<br />
||Zika Virus, de novo design<br />
||2017 - present<br />
|-<br />
|John Bickel<br />
||john.bickel [at] stonybrook [dot] edu<br />
||Doctoral Student<br />
||de novo design<br />
||2019 - present<br />
|-<br />
||Christopher Corbo<br />
||christopher.corbo [at] stonybrook [dot] edu<br />
||Doctoral Student<br />
||Test Set benchmarking, COVID-19<br />
||2019 - present<br />
|-<br />
||Steven Pak<br />
||steven.pak [at] stonybrook [dot] edu<br />
||Doctoral Student<br />
||de novo design, FGFR2, <br />
||2020 - present<br />
|-<br />
||Rodger Tan<br />
||rodger.tan [at] stonybrook [dot] edu<br />
||Undergraduate Student<br />
||Test Set, benchmarking, de novo design<br />
||2019 - present<br />
|-<br />
|Scott Laverty<br />
|scott.laverty [at] stonybrook [dot] edu<br />
|Undergraduate Student<br />
|DOCK6 benchmarking with Autodock4<br />
|2019 - present<br />
|}<br />
<br />
== FORMER MEMBERS ==<br />
{| border="1" cellpadding="8" cellspacing="0" style="background:white; text-align:left; width:90%"<br />
|- style="background:lightgreen"<br />
! style="width 20%" !|Name<br />
! style="width:20%" !|Status<br />
! style="width:20%" !|Project<br />
! style="width:10%" !|Year<br />
! style="width:20%" !|New Position<br />
|-<br />
|Yuchen Zhou<br />
||Doctoral / Masters student<br />
||BoNT/E, DOCK scoring functions, FABP5<br />
||2012 - 2018<br />
|| Postdoc, [http://filizolalab.org/ Filizola Lab] at [https://icahn.mssm.edu/ ISMMS]<br />
|-<br />
|Jiaye Guo<br />
||Doctoral student<br />
||Solvated footprints, Small-molecule inhibitor for HER2<br />
||2013 - 2018<br />
|| Postdoc, [http://www.choderalab.org/ Chodera Lab] at [https://www.mskcc.org/ MSKCC]<br />
|-<br />
|Courtney Singleton<br />
||MD / PhD Student<br />
||HIVgp41, De novo design, genetic algorithm<br />
||2014 - 2018<br />
||Stony Brook Medical School<br />
|-<br />
|Dwight McGee<br />
||Postdoctoral Researcher<br />
||HIVgp41, Free energy calculations, de novo design<br />
||2015 - 2018<br />
|| [http://www.silicontx.com/ Silicon Therapeutics]<br />
|-<br />
|Brian Fochtman<br />
||Doctoral student<br />
||HIVgp41, DOCK development<br />
||2011 - 2017<br />
||The FDA<br />
|-<br />
|Lingling Jiang<br />
||jianglilian68 [at] gmail [dot] com<br />
||HIVgp41, Pharmacophore modeling<br />
||2010 - 2015<br />
||Novo Nordisk<br />
|-<br />
|Brian Ralph<br />
||Undergraduate student<br />
||Fatty acid binding protein, De novo design<br />
||2013 - 2015<br />
||Dental school<br />
|-<br />
|William J. Allen<br />
||Postdoctoral fellow<br />
||HIVgp41, DOCK development<br />
||2011 - 2015<br />
||[http://www.tacc.utexas.edu/ TACC]<br />
|-<br />
|Yulin Huang<br />
||Doctoral student<br />
||EGFR, IGF-IR<br />
||2008 - 2013<br />
||Wall Street<br />
|-<br />
|Sudipto Mukherjee<br />
||Doctoral / Masters student<br />
||DOCK development, HIVgp41<br />
||2005 - 2012<br />
||Postdoc, [http://www.voelzlab.org/ Voelz Lab]<br />
|-<br />
|[http://docking.org/~tbalius/ Trent E. Balius]<br />
||Doctoral student<br />
||EGFR, HIVgp41, DOCK development<br />
||2007 - 2012<br />
||Project Lead, RAS Computational Chemistry Team in the Cancer Research Tecnhology Program (CRTP) at the [https://frederick.cancer.gov/ Frederick National Lab for Cancer Research]<br />
|-<br />
|Patrick Holden<br />
||patrick.m.holden [at] gmail [dot] com<br />
||HIVgp41<br />
||2009 - 2011<br />
|| --<br />
|-<br />
| Jibril Ashiru-Balogun<br />
||Undergraduate student<br />
||HIVgp41<br />
||2010 - 2011<br />
|| --<br />
|-<br />
| Brian Shea<br />
||Undergraduate student<br />
||Kinases <br />
||2010<br />
|| --<br />
|-<br />
| Patrick Murphy<br />
||Undergraduate student<br />
||Influenza <br />
||2009 - 2010<br />
|| --<br />
|-<br />
| Rashi Goyal<br />
||Masters student<br />
||Influenza, HIV <br />
||2007 - 2010<br />
|| --<br />
|-<br />
| Brian McGillick<br />
||Masters student<br />
||HIVgp41<br />
||2007 - 2010<br />
|| --<br />
|-<br />
| Kenneth Ascher<br />
||Undergraduate student<br />
||DOCK method development<br />
||2009 - 2010<br />
|| --<br />
|-<br />
| Dimir Abrar<br />
||Undergraduate student<br />
||HIVRT crossdocking<br />
||2008 - 2009<br />
|| --<br />
|-<br />
| Chetan Raj Rupakheti<br />
||Summer student<br />
||HIVgp41<br />
||2008<br />
|| --<br />
|-<br />
| Bentley Strockbine<br />
||Postdoc <br />
||HIVgp41 <br />
||2005 - 2007<br />
|| --<br />
|-<br />
| Noel Carrascal<br />
||Doctoral student<br />
||DOCK method development<br />
||2005 - 2007<br />
|| --<br />
|-<br />
| Ricky Chachra<br />
||Undergraduate student<br />
||Influenza drug resistance<br />
||2005 - 2007<br />
|| -- <br />
|-<br />
| Amee Patel<br />
||Undergraduate student<br />
||Testset development<br />
||2005 - 2007<br />
|| --<br />
|-<br />
|- <br />
|}</div>Lprentishttps://ringo.ams.stonybrook.edu/index.php?title=2019_Covalent_docking_tutorial_1_with_PDB_5VKG&diff=131742019 Covalent docking tutorial 1 with PDB 5VKG2020-07-20T20:01:53Z<p>Lprentis: </p>
<hr />
<div>This tutorial teaches you how to dock a covalently bound drug molecule to a receptor (PDB 5VKG) using an alpha version of DOCK6.10.<br />
<br />
Use chimera to visualize your system in this case the pdb 5VKG of NMR structure of human Tsg101 UEV in complex with tenatoprazole. <br />
PDB 5VKG consists of 20 different models, but we need only one. Either chose one of the models or ask Lauren to give you the file rcsb104645_model1.pdb. Also ask Lauren to provide you with a necessary version of dock6.<br />
<br />
[[Image:image_starting_structure.png|thumb|center|600px| N16 covalently bound to Tsg101 is shown]]<br />
<br />
<br />
We are interested in the interaction between S atom in Cys 73 and S atom in the ligand. Those two atoms are covalently bonded according to the experimental paper, but Chimera will not show a covalent linker between these two S. We can create the bond ourself in Chimera, if we need (but we don't actually) and measure the distance between these two atoms. If there is a disulfide bond between them, the distance should be 2.05A. <br />
To check the distance we need Shift+Control+left mouse to select two atoms between we want to measure distance. <br />
Tools -> Structure analysis -> Distance. <br />
You will notice the distance from the two sulfurs is about 2.03 angstroms. <br />
<br />
[[Image:Lig_rec2A.png|thumb|center|600px| Distance between the ligand S atom and Cys73 S atom is 2.03A. ]]<br />
<br />
<br />
<br />
== '''I. Receptor Preparation''' ==<br />
<br />
First step is to prepare the receptor. To do this open up the original pdb of the molecule. To prepare the receptor, you need to cut off the covalent linkers to generate the receptor.<br />
Tools -> Structure editing -> Build Structure -> Modify structure - Element S, Bonds 2, Geometry tetrahedral. <br />
The newly formed receptor is now with a complete cysteine. <br />
<br />
[[Image:cys73.png|thumb|center|600px| Receptor with Neutral cysteine. ]]<br />
<br />
Now add hydrogens and charge the protein. To make the cysteine neutral, protons will be added into the system. Protonate with the latest AMBER force field, currently AMBER14SB. <br />
Tools -> Structure editing -> AddH. <br />
Tools -> Structure editing -> AddCharge.<br />
<br />
<br />
To prepare the receptor for making a grid, delete the side chain of the covalently bonded cysteine residue Cys73. When deleting the side chain of the residue make sure to delete S and the beta carbon, but leave the alpha carbon. That is the receptor that will be used for dock grid and docking.<br />
<br />
[[Image:Deleting_cysteine.png|thumb|center|700px| All atoms of the covalently linked cysteine are deleted leaving only the backbone.]]<br />
<br />
== '''II. Ligand Preparation''' ==<br />
<br />
<br />
Open of the original structure rcsb104645_model1.pdb. Delete all the protein leaving only the ligand covalently bonded too the cystine, leave the cystine attached to it. The ligand should be binded to the side chain residue all the way up to the beta carbon. <br />
Chose (holding Control + z) Ligand and Cys -> Invert -> Actions -> Atoms -> delete. <br />
Make Cys73 to be visible in all atom mode.<br />
Chose Cys73 (holding Control + z) -> atom/bond -> show.<br />
<br />
[[Image:Lig bond.png|thumb|center|400px| Ligand and Cys73 in receptor.]]<br />
<br />
Then we create a disulfide bond between S in the ligand and the residue. The command bellow will create a disulfide covalent bond:<br />
Chose S in the ligand and in the Cys73 (control +z).<br />
Preferences -> Command line -> type "bond sel". It will create a disulfide covalent bond. <br />
Protonate the modified ligand.<br />
Tools -> Structure editing -> AddH<br />
<br />
[[Image:Lig h.png|thumb|center|400px| Modified ligand with H.]]<br />
<br />
<br />
Look at N at the backbone on Cys73 residue. There is only one H attached to N after adding hydrogens, but need to be two. So add one more H to N at the Cys aminoacid backbone. To do so chose N (holding Control +z) and go to <br />
Tools -> Structure editing -> Built structure - Modify Structure - Element N - Bonds 3 - Geometry trigonal.<br />
<br />
Next we charge the ligand. <br />
Tools -> Structure editing -> AddCharge -Net charge +1 - with AM1BCC.<br />
<br />
Then delete all of the hydrogens off the beta-carbon.<br />
<br />
[[Image:Lig_CBnoH.png|thumb|center|400px| Ligand with no H on beta-carbon and two Hs at N atom in the backbone.]]<br />
<br />
<br />
Next we need to modify the beta carbon to D2, and modify the side chain sulfur atom to D1. To do so save prepared ligand in mol2 format and open it with a text editing tool. <br />
Then manually change the atom name of the beta carbon to D2 and change the atom type from C.3 to Du. Change the atom name of the gamma sulfur connected to the beta carbon to D1 and changed the atom type to Du as seen below:<br />
@<TRIPOS>ATOM<br />
1 '''D2''' -24.0727 34.9285 -36.1952 '''Du''' 1 LIG -0.0660<br />
2 '''D1''' -25.1580 36.1840 -35.7130 '''Du''' 1 LIG -0.1111<br />
<br />
Delete the backbone of the cysteine leaving the beta carbon.<br />
The ligand should now look like this in chimera:<br />
[[Image:Image_n16_charged_with_dummy_atoms.png|thumb|center|600px| N16 modified to include the beta carbon and sulfur as dummy atoms. ]]<br />
<br />
This is the end of the ligand preparation.<br />
<br />
== '''III. Preparing the sphere files''' ==<br />
<br />
We need to prepare two types of spheres: 1) spheres for orienting the ligand; 2) spheres for box generating .<br />
<br />
The only spheres that will be orientated will be the alpha carbon, beta carbon, and the sulfur on the cysteine sidechain. Open the mol2 file with prepared ligand. Isolate the sulfur, alpha and beta carbons and delete everything else. Save it into lig_abs.mol2.<br />
[[Image:Image_n16_spheres.png|thumb|center|600px| The three atoms from the cysteine sidechain needed for oritenting: beta carbon, alpha carbon, and sulfur.]]<br />
<br />
<br />
Convert saved coordinates in pdb or mol2 into a sphere file: lig_abs.mol2 lig_abs_spheres.sph<br />
<br />
[[Image: Ligabsspheres.png |thumb|center|300px| Spheres for Orienting]]<br />
<br />
Open file lig_abs_spheres.sph with text editor. Spheres in lig_abs_spheres.sph should be in exact order as 1)S gamma 2)C beta 3)C alpha. Check how atoms are oriented in lig_abs.mol2.<br />
@<TRIPOS>ATOM<br />
1 CA -24.6380 34.0060 -37.3390 C.3 1 CYS 0.0000<br />
2 CB -24.0170 34.8640 -36.2200 C.3 1 CYS 0.0000<br />
3 SG -25.1580 36.1840 -35.7130 S.3 1 CYS 0.0000<br />
<br />
It means that in lig_abs_spheres.sph they are also oriented in the same order, but wee need a different order of spheres. Open lig_abs_spheres.sph and rearrange line in correct order by hand.<br />
<br />
<br />
Now spheres will be generated for the box. A sphere file will be made using the coordinates from the ligand file lig_03_06.mol2. Use only heavy atoms to generate spheres.<br />
<br />
<br />
<br />
[[Image: Ligspheres2.png |thumb|center|300px| Spheres for Orienting]]<br />
<br />
== '''IV. Box generating''' ==<br />
<br />
Now that the spheres are generated twice once for orientating and the other for the dock/grid. The box will be generated. <br />
Go to 003.gridbox. Create a file showbox.in. In showbox.in write:<br />
Y<br />
8.0<br />
../002.spheres/lig_spheres.sph <br />
1<br />
lig.box.pdb<br />
<br />
Run the command to generate a box:<br />
showbox < showbox.in<br />
<br />
The box result is shown at Figure below.<br />
[[Image:box1.png |thumb|center|300px| Spheres in box. Heavy atoms in ligand's spheres were used to create a box.]]<br />
<br />
<br />
== '''V. Grid generating''' ==<br />
<br />
Once the box is made the grid can be populated in the box.<br />
Create a file grid.in. But before that copy vdw.defn and chem.defn in current working directory. If don't do this the grid could not recognize the long path for this parameter.<br />
Write below into the grid.in file:<br />
compute_grids yes<br />
grid_spacing 0.4<br />
output_molecule no<br />
contact_score no<br />
energy_score yes<br />
energy_cutoff_distance 9999<br />
atom_model a<br />
attractive_exponent 6<br />
repulsive_exponent 9<br />
distance_dielectric yes<br />
dielectric_factor 4<br />
bump_filter yes<br />
bump_overlap 0.75<br />
receptor_file ../001.files/5VKG_03_06.mol2 change it to ../001.files/5VKG_rec_h.mol2 <br />
box_file lig.box.pdb<br />
vdw_definition_file vdw.defn<br />
chemical_definition_file chem.defn<br />
score_grid_prefix grid<br />
<br />
Run <br />
grid -i grid.in -o grid.out<br />
<br />
If this is successful, you will get following output files.<br />
grid.out<br />
grid.nrg<br />
grid.bmp<br />
<br />
We can begin covalent docking.<br />
<br />
== '''VI. Docking''' ==<br />
Before starting doing docking open all the prepared structures in chimera to visually observe that everything is prepared correctly. Although when everything looks fine, it still doesn't mean that we prepared everything correctly. But if something looks definitely weird, for example the receptor and the box with a ligand are far from each other, we should think about it and redo.<br />
<br />
[[Image:Lig_rec_box.png|thumb|center|300px| Spheres in box. Heavy atoms in ligand's spheres were used to create a box.]]<br />
<br />
We can continue with docking. <br />
Create a file covalent.in and write the following into it.<br />
<br />
conformer_search_type covalent<br />
pruning_use_clustering yes<br />
pruning_max_orients 100<br />
pruning_clustering_cutoff 100<br />
bondlength 1.8<br />
dihedral_step 1.0<br />
pruning_conformer_score_cutoff 100.0<br />
use_clash_overlap no<br />
write_growth_tree no<br />
use_internal_energy yes<br />
Internal_energy_rep_exp 12<br />
internal_energy_cutoff 100.0<br />
ligand_atom_file ../001.files/lig_03_06.mol2<br />
limit_max_ligands no<br />
skip_molecule no<br />
read_mol_solvation no<br />
calculate_rmsd yes<br />
rmsd_reference_filename ../001.files/lig_03_06.mol2<br />
use_database_filter no<br />
orient_ligand yes<br />
automated_matching yes<br />
receptor_site_file ../002.spheres/lig_abs_spheres.sph<br />
max_orientations 1000<br />
critical_points no<br />
chemical_matching no<br />
use_ligand_spheres no<br />
bump_filter no<br />
score_molecules yes<br />
contact_score_primary no<br />
grid_score_primary yes<br />
grid_score_rep_rad_scale 1<br />
grid_score_vdw_scale 1<br />
grid_score_es_scale 1<br />
grid_score_grid_prefix ../003.gridbox/grid<br />
minimize_ligand yes<br />
minimize_anchor no<br />
minimize_flexible_growth yes<br />
use_advanced_simplex_parameters no<br />
simplex_max_cycles 1<br />
simplex_score_converge 0.1<br />
simplex_cycle_converge 1.0<br />
simplex_trans_step 1.0<br />
simplex_rot_step 0.1<br />
simplex_tors_step 10.0<br />
simplex_grow_max_iterations 0<br />
simplex_grow_tors_premin_iterations 1000<br />
simplex_random_seed 0<br />
simplex_restraint_min yes<br />
simplex_coefficient_restraint 10.0<br />
atom_model all<br />
vdw_defn_file ../vdw_AMBER_parm99.defn<br />
flex_defn_file ../flex.defn<br />
flex_drive_file ../flex_drive.tbl<br />
ligand_outfile_prefix covalent_out<br />
write_orientations no<br />
num_scored_conformers 1000<br />
write_conformations no<br />
cluster_conformations yes<br />
cluster_rmsd_threshold 2.0<br />
rank_ligands no<br />
<br />
Run the docking<br />
dock6 -i covalent.in -o covalent.out<br />
<br />
To see the output of docking in chimera <br />
Open Chimera<br />
File -> Open -> 5VKG_rec_h.mol2 (Actions -> Surface -> Show)<br />
File -> Open -> lig_03_06.mol2<br />
<br />
Once everything is loaded go to the ViewDock window and use it's menu to view all the calculated properties regarding the covalent docked ligand by following the steps below.<br />
Tools -> Surface/binding Analysis -> ViewDock -> Select the Covalent Dock output file. (covalent_out_scored.mol2)<br />
In the loaded dialog box select Dock4,5 or 6<br />
Column -> Show -> Grid_Score<br />
Column -> Show -> HA_RMSDs<br />
<br />
[[Image: Dock_result.png|thumb|center|400px| Dock results]]<br />
<br />
<br />
[[Image: Lowest_rmsd_19.png|thumb|center|600px| Docked molecule with the lowest rmsd among all docked poses. Rmsd is 1.9A, -22 Grid score]]<br />
<br />
1.9 RMSD is a sampling success. Is it also a scoring success? To understand it we nee to see which of the molecules was ranked first. TO do this let's open covalent_out_scored.mol2 in text editor and see which ligand is appeared first. If it is a molecule with a lowest RMSD than it is a success, but in our case it is not. It means it is a scoring failure. The lowest RMSD structure is ranked second.<br />
<br />
[[Image: Dock_first.png|thumb|center|400px| Docked molecule with the best scoring. We see it is a scoring failure as it is not a lowest rmsd ligand pose]]</div>Lprentishttps://ringo.ams.stonybrook.edu/index.php?title=2019_Covalent_docking_tutorial_1_with_PDB_5VKG&diff=131732019 Covalent docking tutorial 1 with PDB 5VKG2020-07-20T15:17:44Z<p>Lprentis: </p>
<hr />
<div>This tutorial teaches you how to dock a covalently bound drug molecule to a receptor (PDB 5VKG) using an alpha version of dock6.10.<br />
<br />
Use chimera to visualize your system in this case the pdb 5VKG of NMR structure of human Tsg101 UEV in complex with tenatoprazole. <br />
PDB 5VKG consists of 20 different models, but we need only one. Either chose one of the models or ask Lauren to give you the file rcsb104645_model1.pdb. Also ask Lauren to provide you with a necessary version of dock6.<br />
<br />
[[Image:image_starting_structure.png|thumb|center|600px| N16 covalently bound to Tsg101 is shown]]<br />
<br />
<br />
We are interested in the interaction between S atom in Cys 73 and S atom in the ligand. Those two atoms are covalently bonded according to the experimental paper, but Chimera will not show a covalent linker between these two S. We can create the bond ourself in Chimera, if we need (but we don't actually) and measure the distance between these two atoms. If there is a disulfide bond between them, the distance should be 2.05A. <br />
To check the distance we need Shift+Control+left mouse to select two atoms between we want to measure distance. <br />
Tools -> Structure analysis -> Distance. <br />
You will notice the distance from the two sulfurs is about 2.03 angstroms. <br />
<br />
[[Image:Lig_rec2A.png|thumb|center|600px| Distance between the ligand S atom and Cys73 S atom is 2.03A. ]]<br />
<br />
<br />
<br />
== '''I. Receptor Preparation''' ==<br />
<br />
First step is to prepare the receptor. To do this open up the original pdb of the molecule. To prepare the receptor, you need to cut off the covalent linkers to generate the receptor.<br />
Tools -> Structure editing -> Build Structure -> Modify structure - Element S, Bonds 2, Geometry tetrahedral. <br />
The newly formed receptor is now with a complete cysteine. <br />
<br />
[[Image:cys73.png|thumb|center|600px| Receptor with Neutral cysteine. ]]<br />
<br />
Now add hydrogens and charge the protein. To make the cysteine neutral, protons will be added into the system. Protonate with the latest AMBER force field, currently AMBER14SB. <br />
Tools -> Structure editing -> AddH. <br />
Tools -> Structure editing -> AddCharge.<br />
<br />
<br />
To prepare the receptor for making a grid, delete the side chain of the covalently bonded cysteine residue Cys73. When deleting the side chain of the residue make sure to delete S and the beta carbon, but leave the alpha carbon. That is the receptor that will be used for dock grid and docking.<br />
<br />
[[Image:Deleting_cysteine.png|thumb|center|700px| All atoms of the covalently linked cysteine are deleted leaving only the backbone.]]<br />
<br />
== '''II. Ligand Preparation''' ==<br />
<br />
<br />
Open of the original structure rcsb104645_model1.pdb. Delete all the protein leaving only the ligand covalently bonded too the cystine, leave the cystine attached to it. The ligand should be binded to the side chain residue all the way up to the beta carbon. <br />
Chose (holding Control + z) Ligand and Cys -> Invert -> Actions -> Atoms -> delete. <br />
Make Cys73 to be visible in all atom mode.<br />
Chose Cys73 (holding Control + z) -> atom/bond -> show.<br />
<br />
[[Image:Lig bond.png|thumb|center|400px| Ligand and Cys73 in receptor.]]<br />
<br />
Then we create a disulfide bond between S in the ligand and the residue. The command bellow will create a disulfide covalent bond:<br />
Chose S in the ligand and in the Cys73 (control +z).<br />
Preferences -> Command line -> type "bond sel". It will create a disulfide covalent bond. <br />
Protonate the modified ligand.<br />
Tools -> Structure editing -> AddH<br />
<br />
[[Image:Lig h.png|thumb|center|400px| Modified ligand with H.]]<br />
<br />
<br />
Look at N at the backbone on Cys73 residue. There is only one H attached to N after adding hydrogens, but need to be two. So add one more H to N at the Cys aminoacid backbone. To do so chose N (holding Control +z) and go to <br />
Tools -> Structure editing -> Built structure - Modify Structure - Element N - Bonds 3 - Geometry trigonal.<br />
<br />
Next we charge the ligand. <br />
Tools -> Structure editing -> AddCharge -Net charge +1 - with AM1BCC.<br />
<br />
Then delete all of the hydrogens off the beta-carbon.<br />
<br />
[[Image:Lig_CBnoH.png|thumb|center|400px| Ligand with no H on beta-carbon and two Hs at N atom in the backbone.]]<br />
<br />
<br />
Next we need to modify the beta carbon to D2, and modify the side chain sulfur atom to D1. To do so save prepared ligand in mol2 format and open it with a text editing tool. <br />
Then manually change the atom name of the beta carbon to D2 and change the atom type from C.3 to Du. Change the atom name of the gamma sulfur connected to the beta carbon to D1 and changed the atom type to Du as seen below:<br />
@<TRIPOS>ATOM<br />
1 '''D2''' -24.0727 34.9285 -36.1952 '''Du''' 1 LIG -0.0660<br />
2 '''D1''' -25.1580 36.1840 -35.7130 '''Du''' 1 LIG -0.1111<br />
<br />
Delete the backbone of the cysteine leaving the beta carbon.<br />
The ligand should now look like this in chimera:<br />
[[Image:Image_n16_charged_with_dummy_atoms.png|thumb|center|600px| N16 modified to include the beta carbon and sulfur as dummy atoms. ]]<br />
<br />
This is the end of the ligand preparation.<br />
<br />
== '''III. Preparing the sphere files''' ==<br />
<br />
We need to prepare two types of spheres: 1) spheres for orienting the ligand; 2) spheres for box generating .<br />
<br />
The only spheres that will be orientated will be the alpha carbon, beta carbon, and the sulfur on the cysteine sidechain. Open the mol2 file with prepared ligand. Isolate the sulfur, alpha and beta carbons and delete everything else. Save it into lig_abs.mol2.<br />
[[Image:Image_n16_spheres.png|thumb|center|600px| The three atoms from the cysteine sidechain needed for oritenting: beta carbon, alpha carbon, and sulfur.]]<br />
<br />
<br />
Convert saved coordinates in pdb or mol2 into a sphere file: lig_abs.mol2 lig_abs_spheres.sph<br />
<br />
[[Image: Ligabsspheres.png |thumb|center|300px| Spheres for Orienting]]<br />
<br />
Open file lig_abs_spheres.sph with text editor. Spheres in lig_abs_spheres.sph should be in exact order as 1)S gamma 2)C beta 3)C alpha. Check how atoms are oriented in lig_abs.mol2.<br />
@<TRIPOS>ATOM<br />
1 CA -24.6380 34.0060 -37.3390 C.3 1 CYS 0.0000<br />
2 CB -24.0170 34.8640 -36.2200 C.3 1 CYS 0.0000<br />
3 SG -25.1580 36.1840 -35.7130 S.3 1 CYS 0.0000<br />
<br />
It means that in lig_abs_spheres.sph they are also oriented in the same order, but wee need a different order of spheres. Open lig_abs_spheres.sph and rearrange line in correct order by hand.<br />
<br />
<br />
Now spheres will be generated for the box. A sphere file will be made using the coordinates from the ligand file lig_03_06.mol2. Use only heavy atoms to generate spheres.<br />
<br />
<br />
<br />
[[Image: Ligspheres2.png |thumb|center|300px| Spheres for Orienting]]<br />
<br />
== '''IV. Box generating''' ==<br />
<br />
Now that the spheres are generated twice once for orientating and the other for the dock/grid. The box will be generated. <br />
Go to 003.gridbox. Create a file showbox.in. In showbox.in write:<br />
Y<br />
8.0<br />
../002.spheres/lig_spheres.sph <br />
1<br />
lig.box.pdb<br />
<br />
Run the command to generate a box:<br />
showbox < showbox.in<br />
<br />
The box result is shown at Figure below.<br />
[[Image:box1.png |thumb|center|300px| Spheres in box. Heavy atoms in ligand's spheres were used to create a box.]]<br />
<br />
<br />
== '''V. Grid generating''' ==<br />
<br />
Once the box is made the grid can be populated in the box.<br />
Create a file grid.in. But before that copy vdw.defn and chem.defn in current working directory. If don't do this the grid could not recognize the long path for this parameter.<br />
Write below into the grid.in file:<br />
compute_grids yes<br />
grid_spacing 0.4<br />
output_molecule no<br />
contact_score no<br />
energy_score yes<br />
energy_cutoff_distance 9999<br />
atom_model a<br />
attractive_exponent 6<br />
repulsive_exponent 9<br />
distance_dielectric yes<br />
dielectric_factor 4<br />
bump_filter yes<br />
bump_overlap 0.75<br />
receptor_file ../001.files/5VKG_03_06.mol2 change it to ../001.files/5VKG_rec_h.mol2 <br />
box_file lig.box.pdb<br />
vdw_definition_file vdw.defn<br />
chemical_definition_file chem.defn<br />
score_grid_prefix grid<br />
<br />
Run <br />
grid -i grid.in -o grid.out<br />
<br />
If this is successful, you will get following output files.<br />
grid.out<br />
grid.nrg<br />
grid.bmp<br />
<br />
We can begin covalent docking.<br />
<br />
== '''VI. Docking''' ==<br />
Before starting doing docking open all the prepared structures in chimera to visually observe that everything is prepared correctly. Although when everything looks fine, it still doesn't mean that we prepared everything correctly. But if something looks definitely weird, for example the receptor and the box with a ligand are far from each other, we should think about it and redo.<br />
<br />
[[Image:Lig_rec_box.png|thumb|center|300px| Spheres in box. Heavy atoms in ligand's spheres were used to create a box.]]<br />
<br />
We can continue with docking. <br />
Create a file covalent.in and write the following into it.<br />
<br />
conformer_search_type covalent<br />
pruning_use_clustering yes<br />
pruning_max_orients 100<br />
pruning_clustering_cutoff 100<br />
bondlength 1.8<br />
dihedral_step 1.0<br />
pruning_conformer_score_cutoff 100.0<br />
use_clash_overlap no<br />
write_growth_tree no<br />
use_internal_energy yes<br />
Internal_energy_rep_exp 12<br />
internal_energy_cutoff 100.0<br />
ligand_atom_file ../001.files/lig_03_06.mol2<br />
limit_max_ligands no<br />
skip_molecule no<br />
read_mol_solvation no<br />
calculate_rmsd yes<br />
rmsd_reference_filename ../001.files/lig_03_06.mol2<br />
use_database_filter no<br />
orient_ligand yes<br />
automated_matching yes<br />
receptor_site_file ../002.spheres/lig_abs_spheres.sph<br />
max_orientations 1000<br />
critical_points no<br />
chemical_matching no<br />
use_ligand_spheres no<br />
bump_filter no<br />
score_molecules yes<br />
contact_score_primary no<br />
grid_score_primary yes<br />
grid_score_rep_rad_scale 1<br />
grid_score_vdw_scale 1<br />
grid_score_es_scale 1<br />
grid_score_grid_prefix ../003.gridbox/grid<br />
minimize_ligand yes<br />
minimize_anchor no<br />
minimize_flexible_growth yes<br />
use_advanced_simplex_parameters no<br />
simplex_max_cycles 1<br />
simplex_score_converge 0.1<br />
simplex_cycle_converge 1.0<br />
simplex_trans_step 1.0<br />
simplex_rot_step 0.1<br />
simplex_tors_step 10.0<br />
simplex_grow_max_iterations 0<br />
simplex_grow_tors_premin_iterations 1000<br />
simplex_random_seed 0<br />
simplex_restraint_min yes<br />
simplex_coefficient_restraint 10.0<br />
atom_model all<br />
vdw_defn_file ../vdw_AMBER_parm99.defn<br />
flex_defn_file ../flex.defn<br />
flex_drive_file ../flex_drive.tbl<br />
ligand_outfile_prefix covalent_out<br />
write_orientations no<br />
num_scored_conformers 1000<br />
write_conformations no<br />
cluster_conformations yes<br />
cluster_rmsd_threshold 2.0<br />
rank_ligands no<br />
<br />
Run the docking<br />
dock6 -i covalent.in -o covalent.out<br />
<br />
To see the output of docking in chimera <br />
Open Chimera<br />
File -> Open -> 5VKG_rec_h.mol2 (Actions -> Surface -> Show)<br />
File -> Open -> lig_03_06.mol2<br />
<br />
Once everything is loaded go to the ViewDock window and use it's menu to view all the calculated properties regarding the covalent docked ligand by following the steps below.<br />
Tools -> Surface/binding Analysis -> ViewDock -> Select the Covalent Dock output file. (covalent_out_scored.mol2)<br />
In the loaded dialog box select Dock4,5 or 6<br />
Column -> Show -> Grid_Score<br />
Column -> Show -> HA_RMSDs<br />
<br />
[[Image: Dock_result.png|thumb|center|400px| Dock results]]<br />
<br />
<br />
[[Image: Lowest_rmsd_19.png|thumb|center|600px| Docked molecule with the lowest rmsd among all docked poses. Rmsd is 1.9A, -22 Grid score]]<br />
<br />
1.9 RMSD is a sampling success. Is it also a scoring success? To understand it we nee to see which of the molecules was ranked first. TO do this let's open covalent_out_scored.mol2 in text editor and see which ligand is appeared first. If it is a molecule with a lowest RMSD than it is a success, but in our case it is not. It means it is a scoring failure. The lowest RMSD structure is ranked second.<br />
<br />
[[Image: Dock_first.png|thumb|center|400px| Docked molecule with the best scoring. We see it is a scoring failure as it is not a lowest rmsd ligand pose]]</div>Lprentishttps://ringo.ams.stonybrook.edu/index.php?title=DOCK_DN_Development_Goals&diff=13172DOCK DN Development Goals2020-07-20T15:11:29Z<p>Lprentis: /* Current Coding Progress: */</p>
<hr />
<div>This is the Rizzo lab wiki page for coordinating bugs and progress on the de novo project.<br />
<br><br />
<br />
=== Valgrind clean version of the code on cluster that Rizzo lab should be using: ===<br />
Lauren:<br />
/gpfs/projects/rizzo/zzz.programs/dock6.9_release<br />
This version includes all changes of the merge.<br />
<br />
Path to Generic Fragment Library:<br />
/gpfs/projects/rizzo/leprentis/gen-frags-12<br />
<br />
Path to Frequency Anchors:<br />
/gpfs/projects/rizzo/leprentis/zinc1_ancs_freq<br />
<br><br />
<br />
=== Current Coding Progress: ===<br />
Working on these currently:<br />
<br />
# John: Implement fragment frequency picking as an option<br />
# Chris: Guided FPS <br />
# Lauren: Covalent anchor for denovo growth<br />
# Guilherme: rdkit implementation for logp etc<br />
<br />
<br />
<br />
<br><br />
<br />
Need to be fixed/added:<br />
# add print out anchor with frequency option into fraglib code<br />
# MPI option for each anchor <br />
# aromatic rings<br />
# QED<br />
# fraglib generation chirality issue<br />
# chiral centers <br />
# score_molecules and internal_energy problem (for simple_build)<br />
# HMS needs to fixed when no heavy atoms matching<br />
<br />
<br><br />
<br />
Not working on these right now:<br />
# Addition of "3mer" combination fragment check (post tors check)<br />
# Implement Adjacency Matrix into fraglib/dn (initialize matrix and utilize matrix for graph and random fragment picking)<br />
# Min and Max formal charge to replace absolute value of charge.(Broke everything) Step down as layers of growth proceed (layers 1-3 FC = 4, Layers 4-5 FC = 3, Layers 6-8 FC = 2)<br />
# Capping groups for post growth process (halogens and methyls)<br />
# Incorporate tan pruning as final step (post growth) as user option (replace make_unique script) as database filter not dn<br />
<br />
<br><br />
Completed:<br />
# <strike>Lauren: hbond accept/donor descriptor implementation</strike><br />
# <strike>Chris: increase orienting verbose statistics for dn</strike><br />
# <strike>John: acceptance based on freq of torsenv</strike><br />
# <strike>Lauren&John: secondary torenv check of prune dump molecules and testing</strike><br />
# <strike>Lauren&John: SMILEs and ZINC script (for dn and ga)</strike><br />
# <strike>Lauren: add dn name with date and counter function</strike><br />
# <strike>Lauren: Check MGS+(-50)TAN before and after fingerprinting fix for 663 systems</strike><br />
# <strike>Lauren: determine if random seed is reset for each aps</strike><br />
# <strike>Lauren: Create testset for each dn function </strike><br />
# <strike>Lauren: Test simple build function with merged de novo </strike><br />
# <strike>Lauren&Stephen: clean make_unique script for release</strike><br />
# <strike>Lauren: merge GA into dock/dn </strike><br />
# <strike>Dwight & Lauren: MPI wrapper for 192 processors (8 nodes) for testsets on rizzo cluster </strike><br />
# <strike>Lauren: Create short testsets for denovo frag gen, focused fragment generic for DOCK6.9 release </strike><br />
# <strike>Dwight+Lauren: merge parameter files of de novo with DOCK </strike><br />
# <strike>Lauren: add dn_defn file for separate defn with Hydrogens </strike><br />
# <strike>Lauren: Implement csingleton fix for orienting fragments with less than 3 heavy atoms </strike><br />
# <strike>Lauren: Test bfochtman fix for rotatable bonds within an user defined anchor </strike><br />
# <strike>Lauren: Test csingleton fix for orienting fragments with Du </strike><br />
# <strike>Lauren: Test MGS focused fragment library results with dn paper </strike><br />
# <strike>Stephen: editting script to calculate SMILE string of de novo molecules in OpenBabel </strike><br />
# <strike> Stephen: smooth function cutoff for mw </strike><br />
# <strike> Lauren&John: Rework VS protocol to integrate de novo protocol more smoothly </strike><br />
# <strike> Lauren&John: Fix torsion problem for prune_dump molecules </strike><br />
<br><br />
<br />
=== List of features that we definitely want for the 6.9 release: ===<br />
<br />
{| border="1" cellpadding="8" cellspacing="0" style="background:white; text-align:left; width:90%"<br />
|- style="background:lightblue"<br />
! style="width:75%" !|Task<br />
! style="width:15%" !|Owner<br />
! style="width:10%" !|Complete?<br />
|-<br />
|When minimizing with descriptor score, make sure fingerprint is turned off || xxx ||<br />
|-<br />
|Speed up fingerprint calculations by saving reference ligand as a permanent object || WJA || yep<br />
|-<br />
|Add pre-min conformations to growth trees || WJA || yep<br />
|-<br />
|Add verbose flag options || WJA || yep<br />
|-<br />
|Put molecular properties (RB, MW, etc) in mol2 header || WJA || yep<br />
|-<br />
|Put ensemble properties (RB, MW, etc) output stream at the end of each layer || WJA || yep<br />
|-<br />
|Check formal charge prune || BCF || yep<br />
|-<br />
|Combination of horizontal pruning metrics (let's consider dropping tanimoto prune and just using hungarian prune) || WJA || yep<br />
|-<br />
|Finish implementing growth trees || WJA || yep<br />
|-<br />
|Revisit orienting to make sure it is working as intended || WJA || yep<br />
|-<br />
|Fixed a bug where we were marking scaffold_this_layer as true for any fragment || WJA || yep<br />
|-<br />
|Update random sampling function to use last layer changes in graph function || WJA || yep<br />
|-<br />
|Do that same thing for the exhaustive function || WJA || yep<br />
|-<br />
|I don't think we ever clear the scaf_link_sid vector, we definitely should do that somewhere || WJA || yep<br />
|-<br />
|Update exhaustive to combine all frags into one library, just like graph / random. || WJA || yep<br />
|-<br />
|}<br />
<br><br />
<br />
=== List of features/ideas for future releases: ===<br />
<br />
* Using different references for different layers of dn growth (GFPS protocol) Guided footprint similarity - divide the reference into smaller pieces (layers) to help guide the growth paths more efficiently (i.e. directed growth)<br />
* Stereo centers / volume overlap pruning<br />
* Capping group functions (H, CH3, Halogen)<br />
* Incorporate GA at the end of each layer (not easy)<br />
* Overhaul the simple-build function<br />
* Monte carlo algorithm that checks bond frequency<br />
* Scaling max root / layer size with layer<br />
* Select torenv before selecting fragment. Will need to overhaul fraggraph, will keep us from needing to assemble mols that will not pass torenv.<br />
* Add fragname string to restart and dump files, already done for final and fraglib files.<br />
* Add ZINC name to torenv table<br />
* Unusual behavior during library generation when frequency cutoff == 0<br />
* Print out how many molecules cannot be capped. (Difference between ensemble size and dump.)<br />
* building from anchor 0 -> building from scf.98<br />
* Possible torenv check for dump molecules after capping before printing.<br />
* keep tables of what fragments (and torsion types) are already included in a growing molecule (i.e.e the name string has this info) and only accept a new fragment (or torsion type) within certain ranges and probabilities. In other words use knowledge of chemical makeup probabilities to keep from over including or under including certain fragment and bond types (essentially use datamining to help us only build molecules within certain boundaries)<br />
*De novo design with scaled VDW parameters. Exaggerate them and ramp them down or vice versus. May help to eliminate the anchor and slop or anchor and slosh problem.<br />
<br><br />
<br />
=== List of SB2012 systems that we will use for tests: ===<br />
<br />
For now, let's use 5-15 rotatable bonds inclusive; total = 709 systems ("drug-like" size molecules). De novo paper only used 663 systems that removed 46 systems where the cognate ligand did not fall with a +/-2 formal charge. (5through15 = 709, 5through15_ch2 = 663)<br />
<br />
{5RB = 107; 6RB = 96; 7RB = 103; 8RB = 75; 9RB = 66; 10RB = 75; 11RB = 57; 12RB = 41; 13RB = 38; 14RB = 26; 15RB = 25}<br />
<br />
<br></div>Lprentishttps://ringo.ams.stonybrook.edu/index.php?title=DOCK_DN_Development_Goals&diff=13171DOCK DN Development Goals2020-07-20T15:11:05Z<p>Lprentis: /* Current Coding Progress: */</p>
<hr />
<div>This is the Rizzo lab wiki page for coordinating bugs and progress on the de novo project.<br />
<br><br />
<br />
=== Valgrind clean version of the code on cluster that Rizzo lab should be using: ===<br />
Lauren:<br />
/gpfs/projects/rizzo/zzz.programs/dock6.9_release<br />
This version includes all changes of the merge.<br />
<br />
Path to Generic Fragment Library:<br />
/gpfs/projects/rizzo/leprentis/gen-frags-12<br />
<br />
Path to Frequency Anchors:<br />
/gpfs/projects/rizzo/leprentis/zinc1_ancs_freq<br />
<br><br />
<br />
=== Current Coding Progress: ===<br />
Working on these currently:<br />
<br />
# John: Implement fragment frequency picking as an option<br />
# Chris: Guided FPS <br />
# Lauren: Covalent anchor for denovo growth<br />
# Guilherme: rdkit implementation for logp etc<br />
<br />
<br />
<br />
<br><br />
<br />
Need to be fixed/added:<br />
# add print out anchor with frequency option into fraglib code<br />
# MPI option for each anchor <br />
# aromatic rings<br />
# QED<br />
# fraglib generation chirality issue<br />
# chiral centers <br />
# score_molecules and internal_energy problem (for simple_build)<br />
# HMS needs to fixed when no heavy atoms matching<br />
<br />
<br><br />
<br />
Not working on these right now:<br />
# Addition of "3mer" combination fragment check (post tors check)<br />
# Implement Adjacency Matrix into fraglib/dn (initialize matrix and utilize matrix for graph and random fragment picking)<br />
# Min and Max formal charge to replace absolute value of charge.(Broke everything) Step down as layers of growth proceed (layers 1-3 FC = 4, Layers 4-5 FC = 3, Layers 6-8 FC = 2)<br />
# Capping groups for post growth process (halogens and methyls)<br />
# Incorporate tan pruning as final step (post growth) as user option (replace make_unique script) as database filter not dn<br />
<br />
<br><br />
Completed:<br />
# <strike>Lauren: hbond accept/donor descriptor implementation</strike><br />
# <strike>Chris: increase orienting verbose statistics for dn</strike><br />
# <strike>John: acceptance based on freq of torsenv</strike><br />
# <strike>Lauren&John: secondary torenv check of prune dump molecules and testing</strike><br />
# <strike>Lauren&John: SMILEs and ZINC script (for dn and ga)</strike><br />
# <strike>Lauren: add dn name with date and counter function</strike><br />
# <strike>Lauren: Check MGS+(-50)TAN before and after fingerprinting fix for 663 systems</strike><br />
# <strike>Lauren: determine if random seed is reset for each aps</strike><br />
# <strike>Lauren: Create testset for each dn function </strike><br />
# <strike>Lauren: Test simple build function with merged de novo </strike><br />
# <strike>Lauren&Stephen: clean make_unique script for release</strike><br />
# <strike>Lauren: merge GA into dock/dn </strike><br />
# <strike>Dwight & Lauren: MPI wrapper for 192 processors (8 nodes) for testsets on rizzo cluster </strike><br />
# <strike>Lauren: Create short testsets for denovo frag gen, focused fragment generic for DOCK6.9 release </strike><br />
# <strike>Dwight+Lauren: merge parameter files of de novo with DOCK </strike><br />
# <strike>Lauren: add dn_defn file for separate defn with Hydrogens </strike><br />
# <strike>Lauren: Implement csingleton fix for orienting fragments with less than 3 heavy atoms </strike><br />
# <strike>Lauren: Test bfochtman fix for rotatable bonds within an user defined anchor </strike><br />
# <strike>Lauren: Test csingleton fix for orienting fragments with Du </strike><br />
# <strike>Lauren: Test MGS focused fragment library results with dn paper </strike><br />
# <strike>Stephen: editting script to calculate SMILE string of de novo molecules in OpenBabel </strike><br />
# <strike> Steve: smooth function cutoff for mw </strike><br />
# <strike> Lauren&John: Rework VS protocol to integrate de novo protocol more smoothly </strike><br />
# <strike> Lauren&John: Fix torsion problem for prune_dump molecules </strike><br />
<br><br />
<br />
=== List of features that we definitely want for the 6.9 release: ===<br />
<br />
{| border="1" cellpadding="8" cellspacing="0" style="background:white; text-align:left; width:90%"<br />
|- style="background:lightblue"<br />
! style="width:75%" !|Task<br />
! style="width:15%" !|Owner<br />
! style="width:10%" !|Complete?<br />
|-<br />
|When minimizing with descriptor score, make sure fingerprint is turned off || xxx ||<br />
|-<br />
|Speed up fingerprint calculations by saving reference ligand as a permanent object || WJA || yep<br />
|-<br />
|Add pre-min conformations to growth trees || WJA || yep<br />
|-<br />
|Add verbose flag options || WJA || yep<br />
|-<br />
|Put molecular properties (RB, MW, etc) in mol2 header || WJA || yep<br />
|-<br />
|Put ensemble properties (RB, MW, etc) output stream at the end of each layer || WJA || yep<br />
|-<br />
|Check formal charge prune || BCF || yep<br />
|-<br />
|Combination of horizontal pruning metrics (let's consider dropping tanimoto prune and just using hungarian prune) || WJA || yep<br />
|-<br />
|Finish implementing growth trees || WJA || yep<br />
|-<br />
|Revisit orienting to make sure it is working as intended || WJA || yep<br />
|-<br />
|Fixed a bug where we were marking scaffold_this_layer as true for any fragment || WJA || yep<br />
|-<br />
|Update random sampling function to use last layer changes in graph function || WJA || yep<br />
|-<br />
|Do that same thing for the exhaustive function || WJA || yep<br />
|-<br />
|I don't think we ever clear the scaf_link_sid vector, we definitely should do that somewhere || WJA || yep<br />
|-<br />
|Update exhaustive to combine all frags into one library, just like graph / random. || WJA || yep<br />
|-<br />
|}<br />
<br><br />
<br />
=== List of features/ideas for future releases: ===<br />
<br />
* Using different references for different layers of dn growth (GFPS protocol) Guided footprint similarity - divide the reference into smaller pieces (layers) to help guide the growth paths more efficiently (i.e. directed growth)<br />
* Stereo centers / volume overlap pruning<br />
* Capping group functions (H, CH3, Halogen)<br />
* Incorporate GA at the end of each layer (not easy)<br />
* Overhaul the simple-build function<br />
* Monte carlo algorithm that checks bond frequency<br />
* Scaling max root / layer size with layer<br />
* Select torenv before selecting fragment. Will need to overhaul fraggraph, will keep us from needing to assemble mols that will not pass torenv.<br />
* Add fragname string to restart and dump files, already done for final and fraglib files.<br />
* Add ZINC name to torenv table<br />
* Unusual behavior during library generation when frequency cutoff == 0<br />
* Print out how many molecules cannot be capped. (Difference between ensemble size and dump.)<br />
* building from anchor 0 -> building from scf.98<br />
* Possible torenv check for dump molecules after capping before printing.<br />
* keep tables of what fragments (and torsion types) are already included in a growing molecule (i.e.e the name string has this info) and only accept a new fragment (or torsion type) within certain ranges and probabilities. In other words use knowledge of chemical makeup probabilities to keep from over including or under including certain fragment and bond types (essentially use datamining to help us only build molecules within certain boundaries)<br />
*De novo design with scaled VDW parameters. Exaggerate them and ramp them down or vice versus. May help to eliminate the anchor and slop or anchor and slosh problem.<br />
<br><br />
<br />
=== List of SB2012 systems that we will use for tests: ===<br />
<br />
For now, let's use 5-15 rotatable bonds inclusive; total = 709 systems ("drug-like" size molecules). De novo paper only used 663 systems that removed 46 systems where the cognate ligand did not fall with a +/-2 formal charge. (5through15 = 709, 5through15_ch2 = 663)<br />
<br />
{5RB = 107; 6RB = 96; 7RB = 103; 8RB = 75; 9RB = 66; 10RB = 75; 11RB = 57; 12RB = 41; 13RB = 38; 14RB = 26; 15RB = 25}<br />
<br />
<br></div>Lprentishttps://ringo.ams.stonybrook.edu/index.php?title=Rizzo_Lab_Members_and_Contact_Information&diff=13127Rizzo Lab Members and Contact Information2020-06-17T16:04:07Z<p>Lprentis: /* CURRENT MEMBERS */</p>
<hr />
<div>== CONTACT ==<br />
{| border="1" cellpadding="8" cellspacing="0" style="background:white; text-align:left; width:90%"<br />
|- style="background:white"<br />
! style="width:45%" |Robert C. Rizzo<br />
<br />
Stony Brook University <br />
<br />
Department of Applied Mathematics and Statistics<br />
<br />
Office: Math Tower 1-111<br />
<br />
Lab: Math Tower 3-129<br />
<br />
Stony Brook, NY 11794-3600<br />
<br />
! style="width:45%" |Email: rizzorc [at] gmail [dot] com<br />
<br />
Office: (631) 632-9340<br />
<br />
Lab: (631) 632-8519<br />
<br />
Fax: (631) 632-8490<br />
<br />
Website: rizzolab.org<br />
<br />
Wiki: ringo.ams.sunysb.edu<br />
<br />
|}<br />
<br />
[[Image: Rizzo_lab_2019.png|thumb|center|4000px|'''Current 2019 Rizzo Lab Members:''' ''from left to right'' Stephen, Guilherme, Rodger, Rob, Chris, Hyper Master of DOCK John, Scott, and Lauren]]<br />
<br />
== CURRENT MEMBERS ==<br />
{| border="1" cellpadding="8" cellspacing="0" style="background:white; text-align:left; width:90%"<br />
|- style="background:lightblue"<br />
! style="width:30%" !|Name<br />
! style="width:20%" !|E-mail<br />
! style="width:10%" !|Status<br />
! style="width:20%" !|Project<br />
! style="width:10%" !|Year<br />
|-<br />
|[http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/people/rizzo.html Dr. Robert C. Rizzo]<br />
||rizzorc [at] gmail [dot] com<br />
||Principal investigator<br />
||Group leader<br />
||2004 - present<br />
|-<br />
|[https://www.gduarter.com Guilherme Duarte Ramos Matos]<br />
||Guilherme.duarteramosmatos [at] stonybrook [dot] edu<br />
||Postdoctoral Researcher<br />
||Cheminformatics integration, COVID-19<br />
||2019 - present<br />
|-<br />
|[http://ringo.ams.sunysb.edu/~lprentis/ Lauren Prentis]<br />
||lauren.prentis [at] stonybrook [dot] edu<br />
||Doctoral Student<br />
||Tsg101, de novo design, covalent docking, genetic algorithm<br />
||2016 - present<br />
|-<br />
|Stephen Telehany<br />
||stephen.telehany [at] stonybrook [dot] edu<br />
||Doctoral Student<br />
||Zika Virus, de novo design<br />
||2017 - present<br />
|-<br />
|John Bickel<br />
||john.bickel [at] stonybrook [dot] edu<br />
||Doctoral Student<br />
||de novo design<br />
||2019 - present<br />
|-<br />
||Christopher Corbo<br />
||christopher.corbo [at] stonybrook [dot] edu<br />
||Doctoral Student<br />
||Test Set benchmarking, COVID-19<br />
||2019 - present<br />
|-<br />
||Steven Pak<br />
||steven.pak [at] stonybrook [dot] edu<br />
||Doctoral Student<br />
||de novo design, FGFR2, <br />
||2020 - present<br />
|-<br />
||Rodger Tan<br />
||rodger.tan [at] stonybrook [dot] edu<br />
||Undergraduate Student<br />
||Test Set, benchmarking, de novo design<br />
||2019 - present<br />
|-<br />
|Scott Laverty<br />
|scott.laverty [at] stonybrook [dot] edu<br />
|Undergraduate Student<br />
|DOCK6 benchmarking with Autodock4<br />
|2019 - present<br />
|}<br />
<br />
== FORMER MEMBERS ==<br />
{| border="1" cellpadding="8" cellspacing="0" style="background:white; text-align:left; width:90%"<br />
|- style="background:lightgreen"<br />
! style="width 20%" !|Name<br />
! style="width:20%" !|Status<br />
! style="width:20%" !|Project<br />
! style="width:10%" !|Year<br />
! style="width:20%" !|New Position<br />
|-<br />
|Yuchen Zhou<br />
||Doctoral / Masters student<br />
||BoNT/E, DOCK scoring functions, FABP5<br />
||2012 - 2018<br />
|| Postdoc, [http://filizolalab.org/ Filizola Lab] at [https://icahn.mssm.edu/ ISMMS]<br />
|-<br />
|Jiaye Guo<br />
||Doctoral student<br />
||Solvated footprints, Small-molecule inhibitor for HER2<br />
||2013 - 2018<br />
|| Postdoc, [http://www.choderalab.org/ Chodera Lab] at [https://www.mskcc.org/ MSKCC]<br />
|-<br />
|Courtney Singleton<br />
||MD / PhD Student<br />
||HIVgp41, De novo design, genetic algorithm<br />
||2014 - 2018<br />
||Stony Brook Medical School<br />
|-<br />
|Dwight McGee<br />
||Postdoctoral Researcher<br />
||HIVgp41, Free energy calculations, de novo design<br />
||2015 - 2018<br />
|| [http://www.silicontx.com/ Silicon Therapeutics]<br />
|-<br />
|Brian Fochtman<br />
||Doctoral student<br />
||HIVgp41, DOCK development<br />
||2011 - 2017<br />
||The FDA<br />
|-<br />
|Lingling Jiang<br />
||jianglilian68 [at] gmail [dot] com<br />
||HIVgp41, Pharmacophore modeling<br />
||2010 - 2015<br />
||Novo Nordisk<br />
|-<br />
|Brian Ralph<br />
||Undergraduate student<br />
||Fatty acid binding protein, De novo design<br />
||2013 - 2015<br />
||Dental school<br />
|-<br />
|William J. Allen<br />
||Postdoctoral fellow<br />
||HIVgp41, DOCK development<br />
||2011 - 2015<br />
||[http://www.tacc.utexas.edu/ TACC]<br />
|-<br />
|Yulin Huang<br />
||Doctoral student<br />
||EGFR, IGF-IR<br />
||2008 - 2013<br />
||Wall Street<br />
|-<br />
|Sudipto Mukherjee<br />
||Doctoral / Masters student<br />
||DOCK development, HIVgp41<br />
||2005 - 2012<br />
||Postdoc, [http://www.voelzlab.org/ Voelz Lab]<br />
|-<br />
|[http://docking.org/~tbalius/ Trent E. Balius]<br />
||Doctoral student<br />
||EGFR, HIVgp41, DOCK development<br />
||2007 - 2012<br />
||Project Lead, RAS Computational Chemistry Team in the Cancer Research Tecnhology Program (CRTP) at the [https://frederick.cancer.gov/ Frederick National Lab for Cancer Research]<br />
|-<br />
|Patrick Holden<br />
||patrick.m.holden [at] gmail [dot] com<br />
||HIVgp41<br />
||2009 - 2011<br />
|| --<br />
|-<br />
| Jibril Ashiru-Balogun<br />
||Undergraduate student<br />
||HIVgp41<br />
||2010 - 2011<br />
|| --<br />
|-<br />
| Brian Shea<br />
||Undergraduate student<br />
||Kinases <br />
||2010<br />
|| --<br />
|-<br />
| Patrick Murphy<br />
||Undergraduate student<br />
||Influenza <br />
||2009 - 2010<br />
|| --<br />
|-<br />
| Rashi Goyal<br />
||Masters student<br />
||Influenza, HIV <br />
||2007 - 2010<br />
|| --<br />
|-<br />
| Brian McGillick<br />
||Masters student<br />
||HIVgp41<br />
||2007 - 2010<br />
|| --<br />
|-<br />
| Kenneth Ascher<br />
||Undergraduate student<br />
||DOCK method development<br />
||2009 - 2010<br />
|| --<br />
|-<br />
| Dimir Abrar<br />
||Undergraduate student<br />
||HIVRT crossdocking<br />
||2008 - 2009<br />
|| --<br />
|-<br />
| Chetan Raj Rupakheti<br />
||Summer student<br />
||HIVgp41<br />
||2008<br />
|| --<br />
|-<br />
| Bentley Strockbine<br />
||Postdoc <br />
||HIVgp41 <br />
||2005 - 2007<br />
|| --<br />
|-<br />
| Noel Carrascal<br />
||Doctoral student<br />
||DOCK method development<br />
||2005 - 2007<br />
|| --<br />
|-<br />
| Ricky Chachra<br />
||Undergraduate student<br />
||Influenza drug resistance<br />
||2005 - 2007<br />
|| -- <br />
|-<br />
| Amee Patel<br />
||Undergraduate student<br />
||Testset development<br />
||2005 - 2007<br />
|| --<br />
|-<br />
|- <br />
|}</div>Lprentishttps://ringo.ams.stonybrook.edu/index.php?title=Rizzo_Lab_Members_and_Contact_Information&diff=13126Rizzo Lab Members and Contact Information2020-06-17T14:57:13Z<p>Lprentis: /* CURRENT MEMBERS */</p>
<hr />
<div>== CONTACT ==<br />
{| border="1" cellpadding="8" cellspacing="0" style="background:white; text-align:left; width:90%"<br />
|- style="background:white"<br />
! style="width:45%" |Robert C. Rizzo<br />
<br />
Stony Brook University <br />
<br />
Department of Applied Mathematics and Statistics<br />
<br />
Office: Math Tower 1-111<br />
<br />
Lab: Math Tower 3-129<br />
<br />
Stony Brook, NY 11794-3600<br />
<br />
! style="width:45%" |Email: rizzorc [at] gmail [dot] com<br />
<br />
Office: (631) 632-9340<br />
<br />
Lab: (631) 632-8519<br />
<br />
Fax: (631) 632-8490<br />
<br />
Website: rizzolab.org<br />
<br />
Wiki: ringo.ams.sunysb.edu<br />
<br />
|}<br />
<br />
[[Image: Rizzo_lab_2019.png|thumb|center|4000px|'''Current 2019 Rizzo Lab Members:''' ''from left to right'' Stephen, Guilherme, Rodger, Rob, Chris, Hyper Master of DOCK John, Scott, and Lauren]]<br />
<br />
== CURRENT MEMBERS ==<br />
{| border="1" cellpadding="8" cellspacing="0" style="background:white; text-align:left; width:90%"<br />
|- style="background:lightblue"<br />
! style="width:30%" !|Name<br />
! style="width:20%" !|E-mail<br />
! style="width:10%" !|Status<br />
! style="width:20%" !|Project<br />
! style="width:10%" !|Year<br />
|-<br />
|[http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/people/rizzo.html Dr. Robert C. Rizzo]<br />
||rizzorc [at] gmail [dot] com<br />
||Principal investigator<br />
||Group leader<br />
||2004 - present<br />
|-<br />
|[https://www.gduarter.com Guilherme Duarte Ramos Matos]<br />
||Guilherme.duarteramosmatos [at] stonybrook [dot] edu<br />
||Postdoctoral Researcher<br />
||Cheminformatics integration, COVID-19<br />
||2019 - present<br />
|-<br />
|[http://ringo.ams.sunysb.edu/~lprentis/ Lauren Prentis]<br />
||lauren.prentis [at] stonybrook [dot] edu<br />
||Doctoral Student<br />
||HIV Tsg101, FABP5, de novo design, covalent docking, genetic algorithm<br />
||2016 - present<br />
|-<br />
|Stephen Telehany<br />
||stephen.telehany [at] stonybrook [dot] edu<br />
||Doctoral Student<br />
||Zika Virus, de novo design<br />
||2017 - present<br />
|-<br />
|John Bickel<br />
||john.bickel [at] stonybrook [dot] edu<br />
||Doctoral Student<br />
||de novo design<br />
||2019 - present<br />
|-<br />
||Christopher Corbo<br />
||christopher.corbo [at] stonybrook [dot] edu<br />
||Doctoral Student<br />
||Test Set benchmarking, COVID-19<br />
||2019 - present<br />
|-<br />
||Steven Pak<br />
||steven.pak [at] stonybrook [dot] edu<br />
||Doctoral Student<br />
||de novo design, FGFR2, <br />
||2020 - present<br />
|-<br />
||Rodger Tan<br />
||rodger.tan [at] stonybrook [dot] edu<br />
||Undergraduate Student<br />
||Test Set, benchmarking, de novo design<br />
||2019 - present<br />
|-<br />
|Scott Laverty<br />
|scott.laverty [at] stonybrook [dot] edu<br />
|Undergraduate Student<br />
|DOCK6 benchmarking with Autodock4<br />
|2019 - present<br />
|}<br />
<br />
== FORMER MEMBERS ==<br />
{| border="1" cellpadding="8" cellspacing="0" style="background:white; text-align:left; width:90%"<br />
|- style="background:lightgreen"<br />
! style="width 20%" !|Name<br />
! style="width:20%" !|Status<br />
! style="width:20%" !|Project<br />
! style="width:10%" !|Year<br />
! style="width:20%" !|New Position<br />
|-<br />
|Yuchen Zhou<br />
||Doctoral / Masters student<br />
||BoNT/E, DOCK scoring functions, FABP5<br />
||2012 - 2018<br />
|| Postdoc, [http://filizolalab.org/ Filizola Lab] at [https://icahn.mssm.edu/ ISMMS]<br />
|-<br />
|Jiaye Guo<br />
||Doctoral student<br />
||Solvated footprints, Small-molecule inhibitor for HER2<br />
||2013 - 2018<br />
|| Postdoc, [http://www.choderalab.org/ Chodera Lab] at [https://www.mskcc.org/ MSKCC]<br />
|-<br />
|Courtney Singleton<br />
||MD / PhD Student<br />
||HIVgp41, De novo design, genetic algorithm<br />
||2014 - 2018<br />
||Stony Brook Medical School<br />
|-<br />
|Dwight McGee<br />
||Postdoctoral Researcher<br />
||HIVgp41, Free energy calculations, de novo design<br />
||2015 - 2018<br />
|| [http://www.silicontx.com/ Silicon Therapeutics]<br />
|-<br />
|Brian Fochtman<br />
||Doctoral student<br />
||HIVgp41, DOCK development<br />
||2011 - 2017<br />
||The FDA<br />
|-<br />
|Lingling Jiang<br />
||jianglilian68 [at] gmail [dot] com<br />
||HIVgp41, Pharmacophore modeling<br />
||2010 - 2015<br />
||Novo Nordisk<br />
|-<br />
|Brian Ralph<br />
||Undergraduate student<br />
||Fatty acid binding protein, De novo design<br />
||2013 - 2015<br />
||Dental school<br />
|-<br />
|William J. Allen<br />
||Postdoctoral fellow<br />
||HIVgp41, DOCK development<br />
||2011 - 2015<br />
||[http://www.tacc.utexas.edu/ TACC]<br />
|-<br />
|Yulin Huang<br />
||Doctoral student<br />
||EGFR, IGF-IR<br />
||2008 - 2013<br />
||Wall Street<br />
|-<br />
|Sudipto Mukherjee<br />
||Doctoral / Masters student<br />
||DOCK development, HIVgp41<br />
||2005 - 2012<br />
||Postdoc, [http://www.voelzlab.org/ Voelz Lab]<br />
|-<br />
|[http://docking.org/~tbalius/ Trent E. Balius]<br />
||Doctoral student<br />
||EGFR, HIVgp41, DOCK development<br />
||2007 - 2012<br />
||Project Lead, RAS Computational Chemistry Team in the Cancer Research Tecnhology Program (CRTP) at the [https://frederick.cancer.gov/ Frederick National Lab for Cancer Research]<br />
|-<br />
|Patrick Holden<br />
||patrick.m.holden [at] gmail [dot] com<br />
||HIVgp41<br />
||2009 - 2011<br />
|| --<br />
|-<br />
| Jibril Ashiru-Balogun<br />
||Undergraduate student<br />
||HIVgp41<br />
||2010 - 2011<br />
|| --<br />
|-<br />
| Brian Shea<br />
||Undergraduate student<br />
||Kinases <br />
||2010<br />
|| --<br />
|-<br />
| Patrick Murphy<br />
||Undergraduate student<br />
||Influenza <br />
||2009 - 2010<br />
|| --<br />
|-<br />
| Rashi Goyal<br />
||Masters student<br />
||Influenza, HIV <br />
||2007 - 2010<br />
|| --<br />
|-<br />
| Brian McGillick<br />
||Masters student<br />
||HIVgp41<br />
||2007 - 2010<br />
|| --<br />
|-<br />
| Kenneth Ascher<br />
||Undergraduate student<br />
||DOCK method development<br />
||2009 - 2010<br />
|| --<br />
|-<br />
| Dimir Abrar<br />
||Undergraduate student<br />
||HIVRT crossdocking<br />
||2008 - 2009<br />
|| --<br />
|-<br />
| Chetan Raj Rupakheti<br />
||Summer student<br />
||HIVgp41<br />
||2008<br />
|| --<br />
|-<br />
| Bentley Strockbine<br />
||Postdoc <br />
||HIVgp41 <br />
||2005 - 2007<br />
|| --<br />
|-<br />
| Noel Carrascal<br />
||Doctoral student<br />
||DOCK method development<br />
||2005 - 2007<br />
|| --<br />
|-<br />
| Ricky Chachra<br />
||Undergraduate student<br />
||Influenza drug resistance<br />
||2005 - 2007<br />
|| -- <br />
|-<br />
| Amee Patel<br />
||Undergraduate student<br />
||Testset development<br />
||2005 - 2007<br />
|| --<br />
|-<br />
|- <br />
|}</div>Lprentishttps://ringo.ams.stonybrook.edu/index.php?title=Rizzo_Lab_Members_and_Contact_Information&diff=13125Rizzo Lab Members and Contact Information2020-06-17T14:56:27Z<p>Lprentis: /* CURRENT MEMBERS */</p>
<hr />
<div>== CONTACT ==<br />
{| border="1" cellpadding="8" cellspacing="0" style="background:white; text-align:left; width:90%"<br />
|- style="background:white"<br />
! style="width:45%" |Robert C. Rizzo<br />
<br />
Stony Brook University <br />
<br />
Department of Applied Mathematics and Statistics<br />
<br />
Office: Math Tower 1-111<br />
<br />
Lab: Math Tower 3-129<br />
<br />
Stony Brook, NY 11794-3600<br />
<br />
! style="width:45%" |Email: rizzorc [at] gmail [dot] com<br />
<br />
Office: (631) 632-9340<br />
<br />
Lab: (631) 632-8519<br />
<br />
Fax: (631) 632-8490<br />
<br />
Website: rizzolab.org<br />
<br />
Wiki: ringo.ams.sunysb.edu<br />
<br />
|}<br />
<br />
[[Image: Rizzo_lab_2019.png|thumb|center|4000px|'''Current 2019 Rizzo Lab Members:''' ''from left to right'' Stephen, Guilherme, Rodger, Rob, Chris, Hyper Master of DOCK John, Scott, and Lauren]]<br />
<br />
== CURRENT MEMBERS ==<br />
{| border="1" cellpadding="8" cellspacing="0" style="background:white; text-align:left; width:90%"<br />
|- style="background:lightblue"<br />
! style="width:30%" !|Name<br />
! style="width:20%" !|E-mail<br />
! style="width:10%" !|Status<br />
! style="width:20%" !|Project<br />
! style="width:10%" !|Year<br />
|-<br />
|[http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/people/rizzo.html Dr. Robert C. Rizzo]<br />
||rizzorc [at] gmail [dot] com<br />
||Principal investigator<br />
||Group leader<br />
||2004 - present<br />
|-<br />
|[https://www.gduarter.com Guilherme Duarte Ramos Matos]<br />
||Guilherme.duarteramosmatos [at] stonybrook [dot] edu<br />
||Postdoctoral Researcher<br />
||DOCK6 development<br />
||2019 - present<br />
|-<br />
|[http://ringo.ams.sunysb.edu/~lprentis/ Lauren Prentis]<br />
||lauren.prentis [at] stonybrook [dot] edu<br />
||Doctoral Student<br />
||HIV Tsg101, FABP5, de novo design, covalent docking, genetic algorithm<br />
||2016 - present<br />
|-<br />
|Stephen Telehany<br />
||stephen.telehany [at] stonybrook [dot] edu<br />
||Doctoral Student<br />
||Zika Virus, de novo design<br />
||2017 - present<br />
|-<br />
|John Bickel<br />
||john.bickel [at] stonybrook [dot] edu<br />
||Doctoral Student<br />
||de novo design<br />
||2019 - present<br />
|-<br />
||Christopher Corbo<br />
||christopher.corbo [at] stonybrook [dot] edu<br />
||Doctoral Student<br />
||Test Set benchmarking, COVID-19<br />
||2019 - present<br />
|-<br />
||Steven Pak<br />
||steven.pak [at] stonybrook [dot] edu<br />
||Doctoral Student<br />
||de novo design, FGFR2, <br />
||2020 - present<br />
|-<br />
||Rodger Tan<br />
||rodger.tan [at] stonybrook [dot] edu<br />
||Undergraduate Student<br />
||Test Set, benchmarking, de novo design<br />
||2019 - present<br />
|-<br />
|Scott Laverty<br />
|scott.laverty [at] stonybrook [dot] edu<br />
|Undergraduate Student<br />
|DOCK6 benchmarking with Autodock4<br />
|2019 - present<br />
|}<br />
<br />
== FORMER MEMBERS ==<br />
{| border="1" cellpadding="8" cellspacing="0" style="background:white; text-align:left; width:90%"<br />
|- style="background:lightgreen"<br />
! style="width 20%" !|Name<br />
! style="width:20%" !|Status<br />
! style="width:20%" !|Project<br />
! style="width:10%" !|Year<br />
! style="width:20%" !|New Position<br />
|-<br />
|Yuchen Zhou<br />
||Doctoral / Masters student<br />
||BoNT/E, DOCK scoring functions, FABP5<br />
||2012 - 2018<br />
|| Postdoc, [http://filizolalab.org/ Filizola Lab] at [https://icahn.mssm.edu/ ISMMS]<br />
|-<br />
|Jiaye Guo<br />
||Doctoral student<br />
||Solvated footprints, Small-molecule inhibitor for HER2<br />
||2013 - 2018<br />
|| Postdoc, [http://www.choderalab.org/ Chodera Lab] at [https://www.mskcc.org/ MSKCC]<br />
|-<br />
|Courtney Singleton<br />
||MD / PhD Student<br />
||HIVgp41, De novo design, genetic algorithm<br />
||2014 - 2018<br />
||Stony Brook Medical School<br />
|-<br />
|Dwight McGee<br />
||Postdoctoral Researcher<br />
||HIVgp41, Free energy calculations, de novo design<br />
||2015 - 2018<br />
|| [http://www.silicontx.com/ Silicon Therapeutics]<br />
|-<br />
|Brian Fochtman<br />
||Doctoral student<br />
||HIVgp41, DOCK development<br />
||2011 - 2017<br />
||The FDA<br />
|-<br />
|Lingling Jiang<br />
||jianglilian68 [at] gmail [dot] com<br />
||HIVgp41, Pharmacophore modeling<br />
||2010 - 2015<br />
||Novo Nordisk<br />
|-<br />
|Brian Ralph<br />
||Undergraduate student<br />
||Fatty acid binding protein, De novo design<br />
||2013 - 2015<br />
||Dental school<br />
|-<br />
|William J. Allen<br />
||Postdoctoral fellow<br />
||HIVgp41, DOCK development<br />
||2011 - 2015<br />
||[http://www.tacc.utexas.edu/ TACC]<br />
|-<br />
|Yulin Huang<br />
||Doctoral student<br />
||EGFR, IGF-IR<br />
||2008 - 2013<br />
||Wall Street<br />
|-<br />
|Sudipto Mukherjee<br />
||Doctoral / Masters student<br />
||DOCK development, HIVgp41<br />
||2005 - 2012<br />
||Postdoc, [http://www.voelzlab.org/ Voelz Lab]<br />
|-<br />
|[http://docking.org/~tbalius/ Trent E. Balius]<br />
||Doctoral student<br />
||EGFR, HIVgp41, DOCK development<br />
||2007 - 2012<br />
||Project Lead, RAS Computational Chemistry Team in the Cancer Research Tecnhology Program (CRTP) at the [https://frederick.cancer.gov/ Frederick National Lab for Cancer Research]<br />
|-<br />
|Patrick Holden<br />
||patrick.m.holden [at] gmail [dot] com<br />
||HIVgp41<br />
||2009 - 2011<br />
|| --<br />
|-<br />
| Jibril Ashiru-Balogun<br />
||Undergraduate student<br />
||HIVgp41<br />
||2010 - 2011<br />
|| --<br />
|-<br />
| Brian Shea<br />
||Undergraduate student<br />
||Kinases <br />
||2010<br />
|| --<br />
|-<br />
| Patrick Murphy<br />
||Undergraduate student<br />
||Influenza <br />
||2009 - 2010<br />
|| --<br />
|-<br />
| Rashi Goyal<br />
||Masters student<br />
||Influenza, HIV <br />
||2007 - 2010<br />
|| --<br />
|-<br />
| Brian McGillick<br />
||Masters student<br />
||HIVgp41<br />
||2007 - 2010<br />
|| --<br />
|-<br />
| Kenneth Ascher<br />
||Undergraduate student<br />
||DOCK method development<br />
||2009 - 2010<br />
|| --<br />
|-<br />
| Dimir Abrar<br />
||Undergraduate student<br />
||HIVRT crossdocking<br />
||2008 - 2009<br />
|| --<br />
|-<br />
| Chetan Raj Rupakheti<br />
||Summer student<br />
||HIVgp41<br />
||2008<br />
|| --<br />
|-<br />
| Bentley Strockbine<br />
||Postdoc <br />
||HIVgp41 <br />
||2005 - 2007<br />
|| --<br />
|-<br />
| Noel Carrascal<br />
||Doctoral student<br />
||DOCK method development<br />
||2005 - 2007<br />
|| --<br />
|-<br />
| Ricky Chachra<br />
||Undergraduate student<br />
||Influenza drug resistance<br />
||2005 - 2007<br />
|| -- <br />
|-<br />
| Amee Patel<br />
||Undergraduate student<br />
||Testset development<br />
||2005 - 2007<br />
|| --<br />
|-<br />
|- <br />
|}</div>Lprentishttps://ringo.ams.stonybrook.edu/index.php?title=Rizzo_Lab_Members_and_Contact_Information&diff=13124Rizzo Lab Members and Contact Information2020-06-17T14:55:45Z<p>Lprentis: /* CURRENT MEMBERS */</p>
<hr />
<div>== CONTACT ==<br />
{| border="1" cellpadding="8" cellspacing="0" style="background:white; text-align:left; width:90%"<br />
|- style="background:white"<br />
! style="width:45%" |Robert C. Rizzo<br />
<br />
Stony Brook University <br />
<br />
Department of Applied Mathematics and Statistics<br />
<br />
Office: Math Tower 1-111<br />
<br />
Lab: Math Tower 3-129<br />
<br />
Stony Brook, NY 11794-3600<br />
<br />
! style="width:45%" |Email: rizzorc [at] gmail [dot] com<br />
<br />
Office: (631) 632-9340<br />
<br />
Lab: (631) 632-8519<br />
<br />
Fax: (631) 632-8490<br />
<br />
Website: rizzolab.org<br />
<br />
Wiki: ringo.ams.sunysb.edu<br />
<br />
|}<br />
<br />
[[Image: Rizzo_lab_2019.png|thumb|center|4000px|'''Current 2019 Rizzo Lab Members:''' ''from left to right'' Stephen, Guilherme, Rodger, Rob, Chris, Hyper Master of DOCK John, Scott, and Lauren]]<br />
<br />
== CURRENT MEMBERS ==<br />
{| border="1" cellpadding="8" cellspacing="0" style="background:white; text-align:left; width:90%"<br />
|- style="background:lightblue"<br />
! style="width:30%" !|Name<br />
! style="width:20%" !|E-mail<br />
! style="width:10%" !|Status<br />
! style="width:20%" !|Project<br />
! style="width:10%" !|Year<br />
|-<br />
|[http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/people/rizzo.html Dr. Robert C. Rizzo]<br />
||rizzorc [at] gmail [dot] com<br />
||Principal investigator<br />
||Group leader<br />
||2004 - present<br />
|-<br />
|[https://www.gduarter.com Guilherme Duarte Ramos Matos]<br />
||Guilherme.duarteramosmatos [at] stonybrook [dot] edu<br />
||Postdoctoral Researcher<br />
||DOCK6 development<br />
||2019 - present<br />
|-<br />
|[http://ringo.ams.sunysb.edu/~lprentis/ Lauren Prentis]<br />
||lauren.prentis [at] stonybrook [dot] edu<br />
||Doctoral Student<br />
||HIV gp41, Fatty acid binding protein, de novo design<br />
||2016 - present<br />
|-<br />
|Stephen Telehany<br />
||stephen.telehany [at] stonybrook [dot] edu<br />
||Doctoral Student<br />
||Zika Virus, de novo design<br />
||2017 - present<br />
|-<br />
|John Bickel<br />
||john.bickel [at] stonybrook [dot] edu<br />
||Doctoral Student<br />
||de novo design<br />
||2019 - present<br />
|-<br />
||Christopher Corbo<br />
||christopher.corbo [at] stonybrook [dot] edu<br />
||Doctoral Student<br />
||Test Set benchmarking, COVID-19<br />
||2019 - present<br />
|-<br />
||Steven Pak<br />
||steven.pak [at] stonybrook [dot] edu<br />
||Doctoral Student<br />
||de novo design, FGFR2, <br />
||2020 - present<br />
|-<br />
||Rodger Tan<br />
||rodger.tan [at] stonybrook [dot] edu<br />
||Undergraduate Student<br />
||Test Set, benchmarking, de novo design<br />
||2019 - present<br />
|-<br />
|Scott Laverty<br />
|scott.laverty [at] stonybrook [dot] edu<br />
|Undergraduate Student<br />
|DOCK6 benchmarking with Autodock4<br />
|2019 - present<br />
|}<br />
<br />
== FORMER MEMBERS ==<br />
{| border="1" cellpadding="8" cellspacing="0" style="background:white; text-align:left; width:90%"<br />
|- style="background:lightgreen"<br />
! style="width 20%" !|Name<br />
! style="width:20%" !|Status<br />
! style="width:20%" !|Project<br />
! style="width:10%" !|Year<br />
! style="width:20%" !|New Position<br />
|-<br />
|Yuchen Zhou<br />
||Doctoral / Masters student<br />
||BoNT/E, DOCK scoring functions, FABP5<br />
||2012 - 2018<br />
|| Postdoc, [http://filizolalab.org/ Filizola Lab] at [https://icahn.mssm.edu/ ISMMS]<br />
|-<br />
|Jiaye Guo<br />
||Doctoral student<br />
||Solvated footprints, Small-molecule inhibitor for HER2<br />
||2013 - 2018<br />
|| Postdoc, [http://www.choderalab.org/ Chodera Lab] at [https://www.mskcc.org/ MSKCC]<br />
|-<br />
|Courtney Singleton<br />
||MD / PhD Student<br />
||HIVgp41, De novo design, genetic algorithm<br />
||2014 - 2018<br />
||Stony Brook Medical School<br />
|-<br />
|Dwight McGee<br />
||Postdoctoral Researcher<br />
||HIVgp41, Free energy calculations, de novo design<br />
||2015 - 2018<br />
|| [http://www.silicontx.com/ Silicon Therapeutics]<br />
|-<br />
|Brian Fochtman<br />
||Doctoral student<br />
||HIVgp41, DOCK development<br />
||2011 - 2017<br />
||The FDA<br />
|-<br />
|Lingling Jiang<br />
||jianglilian68 [at] gmail [dot] com<br />
||HIVgp41, Pharmacophore modeling<br />
||2010 - 2015<br />
||Novo Nordisk<br />
|-<br />
|Brian Ralph<br />
||Undergraduate student<br />
||Fatty acid binding protein, De novo design<br />
||2013 - 2015<br />
||Dental school<br />
|-<br />
|William J. Allen<br />
||Postdoctoral fellow<br />
||HIVgp41, DOCK development<br />
||2011 - 2015<br />
||[http://www.tacc.utexas.edu/ TACC]<br />
|-<br />
|Yulin Huang<br />
||Doctoral student<br />
||EGFR, IGF-IR<br />
||2008 - 2013<br />
||Wall Street<br />
|-<br />
|Sudipto Mukherjee<br />
||Doctoral / Masters student<br />
||DOCK development, HIVgp41<br />
||2005 - 2012<br />
||Postdoc, [http://www.voelzlab.org/ Voelz Lab]<br />
|-<br />
|[http://docking.org/~tbalius/ Trent E. Balius]<br />
||Doctoral student<br />
||EGFR, HIVgp41, DOCK development<br />
||2007 - 2012<br />
||Project Lead, RAS Computational Chemistry Team in the Cancer Research Tecnhology Program (CRTP) at the [https://frederick.cancer.gov/ Frederick National Lab for Cancer Research]<br />
|-<br />
|Patrick Holden<br />
||patrick.m.holden [at] gmail [dot] com<br />
||HIVgp41<br />
||2009 - 2011<br />
|| --<br />
|-<br />
| Jibril Ashiru-Balogun<br />
||Undergraduate student<br />
||HIVgp41<br />
||2010 - 2011<br />
|| --<br />
|-<br />
| Brian Shea<br />
||Undergraduate student<br />
||Kinases <br />
||2010<br />
|| --<br />
|-<br />
| Patrick Murphy<br />
||Undergraduate student<br />
||Influenza <br />
||2009 - 2010<br />
|| --<br />
|-<br />
| Rashi Goyal<br />
||Masters student<br />
||Influenza, HIV <br />
||2007 - 2010<br />
|| --<br />
|-<br />
| Brian McGillick<br />
||Masters student<br />
||HIVgp41<br />
||2007 - 2010<br />
|| --<br />
|-<br />
| Kenneth Ascher<br />
||Undergraduate student<br />
||DOCK method development<br />
||2009 - 2010<br />
|| --<br />
|-<br />
| Dimir Abrar<br />
||Undergraduate student<br />
||HIVRT crossdocking<br />
||2008 - 2009<br />
|| --<br />
|-<br />
| Chetan Raj Rupakheti<br />
||Summer student<br />
||HIVgp41<br />
||2008<br />
|| --<br />
|-<br />
| Bentley Strockbine<br />
||Postdoc <br />
||HIVgp41 <br />
||2005 - 2007<br />
|| --<br />
|-<br />
| Noel Carrascal<br />
||Doctoral student<br />
||DOCK method development<br />
||2005 - 2007<br />
|| --<br />
|-<br />
| Ricky Chachra<br />
||Undergraduate student<br />
||Influenza drug resistance<br />
||2005 - 2007<br />
|| -- <br />
|-<br />
| Amee Patel<br />
||Undergraduate student<br />
||Testset development<br />
||2005 - 2007<br />
|| --<br />
|-<br />
|- <br />
|}</div>Lprentishttps://ringo.ams.stonybrook.edu/index.php?title=Rizzo_Lab_Members_and_Contact_Information&diff=13123Rizzo Lab Members and Contact Information2020-06-17T14:54:15Z<p>Lprentis: /* CURRENT MEMBERS */</p>
<hr />
<div>== CONTACT ==<br />
{| border="1" cellpadding="8" cellspacing="0" style="background:white; text-align:left; width:90%"<br />
|- style="background:white"<br />
! style="width:45%" |Robert C. Rizzo<br />
<br />
Stony Brook University <br />
<br />
Department of Applied Mathematics and Statistics<br />
<br />
Office: Math Tower 1-111<br />
<br />
Lab: Math Tower 3-129<br />
<br />
Stony Brook, NY 11794-3600<br />
<br />
! style="width:45%" |Email: rizzorc [at] gmail [dot] com<br />
<br />
Office: (631) 632-9340<br />
<br />
Lab: (631) 632-8519<br />
<br />
Fax: (631) 632-8490<br />
<br />
Website: rizzolab.org<br />
<br />
Wiki: ringo.ams.sunysb.edu<br />
<br />
|}<br />
<br />
[[Image: Rizzo_lab_2019.png|thumb|center|4000px|'''Current 2019 Rizzo Lab Members:''' ''from left to right'' Stephen, Guilherme, Rodger, Rob, Chris, Hyper Master of DOCK John, Scott, and Lauren]]<br />
<br />
== CURRENT MEMBERS ==<br />
{| border="1" cellpadding="8" cellspacing="0" style="background:white; text-align:left; width:90%"<br />
|- style="background:lightblue"<br />
! style="width:30%" !|Name<br />
! style="width:20%" !|E-mail<br />
! style="width:10%" !|Status<br />
! style="width:20%" !|Project<br />
! style="width:10%" !|Year<br />
|-<br />
|[http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/people/rizzo.html Dr. Robert C. Rizzo]<br />
||rizzorc [at] gmail [dot] com<br />
||Principal investigator<br />
||Group leader<br />
||2004 - present<br />
|-<br />
|[https://www.gduarter.com Guilherme Duarte Ramos Matos]<br />
||Guilherme.duarteramosmatos [at] stonybrook [dot] edu<br />
||Postdoctoral Researcher<br />
||DOCK6 development<br />
||2019 - present<br />
|-<br />
|[http://ringo.ams.sunysb.edu/~lprentis/ Lauren Prentis]<br />
||lauren.prentis [at] stonybrook [dot] edu<br />
||Doctoral Student<br />
||HIV gp41, Fatty acid binding protein, de novo design<br />
||2016 - present<br />
|-<br />
|Stephen Telehany<br />
||stephen.telehany [at] stonybrook [dot] edu<br />
||Doctoral Student<br />
||Zika Virus, de novo design<br />
||2017 - present<br />
|-<br />
|John Bickel<br />
||john.bickel [at] stonybrook [dot] edu<br />
||Doctoral Student<br />
||de novo design<br />
||2019 - present<br />
|-<br />
||Christopher Corbo<br />
||christopher.corbo [at] stonybrook [dot] edu<br />
||Doctoral Student<br />
||Test Set benchmarking, COVID-19<br />
||2019 - present<br />
|-<br />
||Steven Pak<br />
||steven.pak [at] stonybrook [dot] edu<br />
||Doctoral Student<br />
||Test Set benchmarking, xlogp<br />
||2020 - present<br />
|-<br />
||Rodger Tan<br />
||rodger.tan [at] stonybrook [dot] edu<br />
||Undergraduate Student<br />
||Test Set, benchmarking, de novo design<br />
||2019 - present<br />
|-<br />
|Scott Laverty<br />
|scott.laverty [at] stonybrook [dot] edu<br />
|Undergraduate Student<br />
|DOCK6 benchmarking with Autodock4<br />
|2019 - present<br />
|}<br />
<br />
== FORMER MEMBERS ==<br />
{| border="1" cellpadding="8" cellspacing="0" style="background:white; text-align:left; width:90%"<br />
|- style="background:lightgreen"<br />
! style="width 20%" !|Name<br />
! style="width:20%" !|Status<br />
! style="width:20%" !|Project<br />
! style="width:10%" !|Year<br />
! style="width:20%" !|New Position<br />
|-<br />
|Yuchen Zhou<br />
||Doctoral / Masters student<br />
||BoNT/E, DOCK scoring functions, FABP5<br />
||2012 - 2018<br />
|| Postdoc, [http://filizolalab.org/ Filizola Lab] at [https://icahn.mssm.edu/ ISMMS]<br />
|-<br />
|Jiaye Guo<br />
||Doctoral student<br />
||Solvated footprints, Small-molecule inhibitor for HER2<br />
||2013 - 2018<br />
|| Postdoc, [http://www.choderalab.org/ Chodera Lab] at [https://www.mskcc.org/ MSKCC]<br />
|-<br />
|Courtney Singleton<br />
||MD / PhD Student<br />
||HIVgp41, De novo design, genetic algorithm<br />
||2014 - 2018<br />
||Stony Brook Medical School<br />
|-<br />
|Dwight McGee<br />
||Postdoctoral Researcher<br />
||HIVgp41, Free energy calculations, de novo design<br />
||2015 - 2018<br />
|| [http://www.silicontx.com/ Silicon Therapeutics]<br />
|-<br />
|Brian Fochtman<br />
||Doctoral student<br />
||HIVgp41, DOCK development<br />
||2011 - 2017<br />
||The FDA<br />
|-<br />
|Lingling Jiang<br />
||jianglilian68 [at] gmail [dot] com<br />
||HIVgp41, Pharmacophore modeling<br />
||2010 - 2015<br />
||Novo Nordisk<br />
|-<br />
|Brian Ralph<br />
||Undergraduate student<br />
||Fatty acid binding protein, De novo design<br />
||2013 - 2015<br />
||Dental school<br />
|-<br />
|William J. Allen<br />
||Postdoctoral fellow<br />
||HIVgp41, DOCK development<br />
||2011 - 2015<br />
||[http://www.tacc.utexas.edu/ TACC]<br />
|-<br />
|Yulin Huang<br />
||Doctoral student<br />
||EGFR, IGF-IR<br />
||2008 - 2013<br />
||Wall Street<br />
|-<br />
|Sudipto Mukherjee<br />
||Doctoral / Masters student<br />
||DOCK development, HIVgp41<br />
||2005 - 2012<br />
||Postdoc, [http://www.voelzlab.org/ Voelz Lab]<br />
|-<br />
|[http://docking.org/~tbalius/ Trent E. Balius]<br />
||Doctoral student<br />
||EGFR, HIVgp41, DOCK development<br />
||2007 - 2012<br />
||Project Lead, RAS Computational Chemistry Team in the Cancer Research Tecnhology Program (CRTP) at the [https://frederick.cancer.gov/ Frederick National Lab for Cancer Research]<br />
|-<br />
|Patrick Holden<br />
||patrick.m.holden [at] gmail [dot] com<br />
||HIVgp41<br />
||2009 - 2011<br />
|| --<br />
|-<br />
| Jibril Ashiru-Balogun<br />
||Undergraduate student<br />
||HIVgp41<br />
||2010 - 2011<br />
|| --<br />
|-<br />
| Brian Shea<br />
||Undergraduate student<br />
||Kinases <br />
||2010<br />
|| --<br />
|-<br />
| Patrick Murphy<br />
||Undergraduate student<br />
||Influenza <br />
||2009 - 2010<br />
|| --<br />
|-<br />
| Rashi Goyal<br />
||Masters student<br />
||Influenza, HIV <br />
||2007 - 2010<br />
|| --<br />
|-<br />
| Brian McGillick<br />
||Masters student<br />
||HIVgp41<br />
||2007 - 2010<br />
|| --<br />
|-<br />
| Kenneth Ascher<br />
||Undergraduate student<br />
||DOCK method development<br />
||2009 - 2010<br />
|| --<br />
|-<br />
| Dimir Abrar<br />
||Undergraduate student<br />
||HIVRT crossdocking<br />
||2008 - 2009<br />
|| --<br />
|-<br />
| Chetan Raj Rupakheti<br />
||Summer student<br />
||HIVgp41<br />
||2008<br />
|| --<br />
|-<br />
| Bentley Strockbine<br />
||Postdoc <br />
||HIVgp41 <br />
||2005 - 2007<br />
|| --<br />
|-<br />
| Noel Carrascal<br />
||Doctoral student<br />
||DOCK method development<br />
||2005 - 2007<br />
|| --<br />
|-<br />
| Ricky Chachra<br />
||Undergraduate student<br />
||Influenza drug resistance<br />
||2005 - 2007<br />
|| -- <br />
|-<br />
| Amee Patel<br />
||Undergraduate student<br />
||Testset development<br />
||2005 - 2007<br />
|| --<br />
|-<br />
|- <br />
|}</div>Lprentishttps://ringo.ams.stonybrook.edu/index.php?title=DOCK_GA_Development_Goals&diff=13122DOCK GA Development Goals2020-06-09T16:05:53Z<p>Lprentis: </p>
<hr />
<div>{| border="1" cellpadding="8" cellspacing="0" style="background:white; text-align:left; width:90%"<br />
|- style="background:lightblue"<br />
! style="width:75%" !|Tasks<br />
! style="width:25%" !|src<br />
! style="width:13%" !|Owner<br />
! style="width:10%" !|Complete?<br />
|-<br />
|Fix bug that collapsed atom coordinates || everywhere? nowhere? somewhere. || LEP || yes<br />
|-<br />
|Added Delimeter header ||conf_gen_ga || LEP || Yes<br />
|-<br />
|Fix xover only feature ||conf_gen_ga || LEP || Yes<br />
|-<br />
|Put in error messages for mut_rate > 1 || conf_gen_ga ||LEP || Yes<br />
|-<br />
|Manual user-defined mutation type ||conf_gen_ga || LEP || Yes<br />
|-<br />
|Remove check only option || conf_gen_ga || LEP || Yes<br />
|-<br />
|Add single molecule evolution in testcase in install dir. || install/test/genetic || LEP ||no<br />
|-<br />
|Compute delta slope of fitness score || congen_ga.cpp || LEP ||no<br />
|}<br />
<br><br />
<br />
<br />
==To Do List==<br />
# slow down molecular evolution so there are less drastic canges between each successive generation<br />
# tanimoto coefficient percent change - might be inaccurate due to tan coef behavior<br />
# Rotatable bond changes<br />
# Number of aromatic rings <br />
#-xover (guided based on score) - Good v Good ; Bad v Good ; Bad v Bad THIS <br />
#nonexhaustive xover (pick subset of xover based on probability)<br />
#2-3 point xover at once<br />
#adaptive maintenance ensemble based on ensemble convergence THIS<br />
#bring in new parents based on convergence<br />
#Mutations-<br />
##adaptive mutation rate THIS<br />
##pick location of mutation based on something<br />
##pick mutation type based on behavior of ensemble<br />
##molecules too large boost deletion<br />
##molecules too small, add more groups<br />
##change ...boost replace/sub<br />
##mutation type selection based on probability vs ensemble<br />
##complete x # y mutation so far so less prevalent etc<br />
##3 layer subs do no work so don't do them<br />
##replace > 1 segment<br />
#fitness-<br />
##turn on and off niching adaptive/extinction<br />
##reduce boost of fragments and all poor mols with niching<br />
##pareto/mulitobjective ga<br />
#selection-<br />
##metropolis selection for tournament/roulette<br />
##adaptive keep #p and #o<br />
#extinction- <br />
##user defined point vs on-the-fly convergence THIS<br />
#stop-<br />
##convergence<br />
#which molecules are best-<br />
##best first pruning - now uses descriptor score even if niching ned to delta to fitness/niching when used<br />
## geometric diversity using Hingarian and Tan pruning</div>Lprentishttps://ringo.ams.stonybrook.edu/index.php?title=DOCK_GA_Development_Goals&diff=13121DOCK GA Development Goals2020-06-09T16:00:40Z<p>Lprentis: </p>
<hr />
<div>{| border="1" cellpadding="8" cellspacing="0" style="background:white; text-align:left; width:90%"<br />
|- style="background:lightblue"<br />
! style="width:75%" !|Tasks<br />
! style="width:25%" !|src<br />
! style="width:13%" !|Owner<br />
! style="width:10%" !|Complete?<br />
|-<br />
|Fix bug that collapsed atom coordinates || everywhere? nowhere? somewhere. || LEP || yes<br />
|-<br />
|Added Delimeter header ||conf_gen_ga || LEP || Yes<br />
|-<br />
|Fix xover only feature ||conf_gen_ga || LEP || Yes<br />
|-<br />
|Put in error messages for mut_rate > 1 || conf_gen_ga ||LEP || Yes<br />
|-<br />
|Manual user-defined mutation type ||conf_gen_ga || LEP || Yes<br />
|-<br />
|Remove check only option || conf_gen_ga || LEP || Yes<br />
|-<br />
|Add single molecule evolution in testcase in install dir. || install/test/genetic || LEP ||no<br />
|}<br />
<br><br />
<br />
<br />
==To Do List==<br />
# slow down molecular evolution so there are less drastic canges between each successive generation<br />
# tanimoto coefficient percent change - might be inaccurate due to tan coef behavior<br />
# Rotatable bond changes<br />
# Number of aromatic rings <br />
#-xover (guided based on score) - Good v Good ; Bad v Good ; Bad v Bad THIS <br />
#nonexhaustive xover (pick subset of xover based on probability)<br />
#2-3 point xover at once<br />
#adaptive maintenance ensemble based on ensemble convergence THIS<br />
#bring in new parents based on convergence<br />
#Mutations-<br />
##adaptive mutation rate THIS<br />
##pick location of mutation based on something<br />
##pick mutation type based on behavior of ensemble<br />
##molecules too large boost deletion<br />
##molecules too small, add more groups<br />
##change ...boost replace/sub<br />
##mutation type selection based on probability vs ensemble<br />
##complete x # y mutation so far so less prevalent etc<br />
##3 layer subs do no work so don't do them<br />
##replace > 1 segment<br />
#fitness-<br />
##turn on and off niching adaptive/extinction<br />
##reduce boost of fragments and all poor mols with niching<br />
##pareto/mulitobjective ga<br />
#selection-<br />
##metropolis selection for tournament/roulette<br />
##adaptive keep #p and #o<br />
#extinction- <br />
##user defined point vs on-the-fly convergence THIS<br />
#stop-<br />
##convergence<br />
#which molecules are best-<br />
##best first pruning - now uses descriptor score even if niching ned to delta to fitness/niching when used<br />
## geometric diversity using Hingarian and Tan pruning</div>Lprentishttps://ringo.ams.stonybrook.edu/index.php?title=2020_AMS-536_Spring_(revised_syllabus)&diff=131162020 AMS-536 Spring (revised syllabus)2020-04-27T20:29:37Z<p>Lprentis: </p>
<hr />
<div><div style="text-align: center;"><br />
'''THIS IS A REVISED SYLLABUS, PLEASE SEE REVISED SYLLABUS NOTES BELOW'''<br><br />
'''THIS IS A REVISED SYLLABUS, PLEASE SEE REVISED SYLLABUS NOTES BELOW'''<br><br />
'''THIS IS A REVISED SYLLABUS, PLEASE SEE REVISED SYLLABUS NOTES BELOW'''<br><br />
'''THIS IS A REVISED SYLLABUS, PLEASE SEE REVISED SYLLABUS NOTES BELOW'''<br><br />
</div><br />
<br />
<br><br />
{| align="center" border="2" cellpadding="8" cellspacing="0" style="background:white; text-align:left; width:80%"<br />
|- style="background:white" ! style="width:10%" <br />
| '''Supervisor''' || Dr. Robert C. Rizzo [631-632-9340, robert dot rizzo -at- stonybrook.edu]<br />
|-<br />
| '''Instructor''' || Dr. Guilherme Duarte Ramos Matos [631-632-8519, guilherme dot duarteramosmatos -at- stonybrook dot edu]<br />
|-<br />
| '''Teaching Assistant''' || Steve Telehany [631-632-8519, stephen dot telehany - at - stonybrook dot edu]<br />
|-<br />
| '''Course No.''' || AMS-536 / CHE-536<br />
|-<br />
| '''Location/Time''' || Math Tower, Room S235 (COMPUTER LAB next to SINC site), Mon/Wed 2:30PM - 3:50PM <br />
|-<br />
| '''Office Hours''' || By appointment, Math Tower, Room 3-129, Dept. of Applied Math & Statistics<br />
|-<br />
| '''Acknowledgments''' || The AMS-536 instructors would like to thank: <br><br />
(1) Chemical Computing Group at http://www.chemcomp.com for generously providing MOE software teaching licenses <br><br />
(2) Firat Coskun and the LI-RED and SEAWULF team for cluster support <br><br />
(3) Pat Tonra for Mathlab support <br><br />
(4) Victor Poon for other computational support<br><br />
|-<br />
| '''Grading''' || Grades will be based on the quality of: <br><br />
(1) attendance, participation in class discussion, wiki tutorial construction, assisting others (25%) <br><br />
(2) oral presentations (25%) <br><br />
(3) final written report (50%)<br />
|-<br />
|}<br />
<br><br />
<br><br />
<br />
== Revised Syllabus Notes ==<br />
As a result of the COVID-19 outbreak the course syllabus has been revised per University guidelines to address the semester being shortened by one week and document changes necessary to teach the course online for the rest of the semester. A brief summary of the changes include:<br />
<br />
<br>(0) The course grading criteria has been modified (see grading breakdown above).<br />
<br>(1) The schedule has been revised starting March 23 2020.<br />
<br>(2) We will continue to hold class at the regularly scheduled time however this will now be done online via the Zoom program ( https://it.stonybrook.edu/services/zoom ).<br />
<br>(3) AMBER tutorials are being prerecorded by the Instructors and will be uploaded as appropriate into the course schedule as online videos. <br />
<br>(4) AMBER tutorials should be viewed online before each relevant Zoom meetings so that meeting time can be spent troubleshooting and providing other guidance as necessary for class tutorials.<br />
<br>(5) Class time normally devoted to watching and evaluating Oral Presentations will instead be used for Zoom meetings devoted to troubleshooting and providing other guidance as necessary for Class Projects.<br />
<br>(6) Oral Presentations of Class Projects will be recorded by each participant individually (see Recording Your Oral Presentation Using Zoom section below), at home, and then emailed to the Instructors (see Video Presentation due date below).<br />
<br>(7) Oral Presentations of Class Projects will be evaluated by 3 course participants and a [http://ringo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2020_ams.536.presentation.assessment.docx Presentation Assessment Sheet] for each talk evaluated will be submitted based on the Reviewer Assignments outlined below.<br />
<br>(8) The Student Accessibility Support Center Statement (see below) has been updated<br />
<br>(9) A Faculty Technical Support Statement (see below) has been added<br />
<br />
== Project Information ==<br />
<br />
'''Student Project Proposal OHARE Sheet'''<br />
*[http://ringo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Projects/studentproject.OHARE.template.docx studentproject.OHARE.template.docx]<br />
<br />
<br />
'''Oral Presentation Guidelines:''' These meetings should be formal and your chance to tell a complete story. Talks should be presented in PPT format and be between 20 and 30 minutes long. The purpose of your talks is for you to clearly and concisely present your overall progress to date including appropriate background material and interpretation of your results. Check our guidelines on [http://ringo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Projects/how_not_to_make_a_presentation.pdf how not to make a presentation]. Talks should be arranged in the following order:<br />
*Introduction/Background (include biological relevance)<br />
*Specifics of Your System<br />
*Computational Details (theory) <br />
*Computational Details (system setup) <br />
*Results and Discussion (include a critical interpretation of your results)<br />
*Conclusions <br />
*Future <br />
*Acknowledgments<br />
<br />
<br />
'''Recording Your Oral Presentation Using Zoom:''' It is very straightforward to create a video of yourself giving a PPT presentation using Zoom:<br />
<br />
*Download the Zoom app ( https://it.stonybrook.edu/services/zoom )<br />
*Open the Zoom app<br />
*Create a new Zoom meeting with only yourself (make sure audio and video are turned on)<br />
*Share your screen<br />
*Open your presentation in PPT and put in presentation mode<br />
*Start recording and give a short test presentation to make sure that everything is working smoothly (use mouse as necessary to highlight specific regions of your slides)<br />
*Stop recording and quit the meeting <br />
*Open the newly created video (using QuickTime or some other video player) to make sure that your test presentation has both audio and video and looks good<br />
*Follow the above steps to create your "full-length" video presentation (videos should not exceed 20 minutes)<br />
*Email your video to the Instructors who will make it available to the class (please name your Zoom video Lastname.mp4)<br />
<br />
<br />
'''Final Written Report Guidelines and Example Final Papers:''' Written project guidelines and example papers to use as a guide are provided below.<br />
*[http://ringo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Projects/project.guidelines.pdf project.guidelines.pdf]<br />
*[http://ringo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Projects/project.example.dGhyd.pdf project.example.dGhyd.pdf]<br />
*[http://ringo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Projects/project.example.MMPS.pdf project.example.MMPS.pdf]<br />
<br><br />
<br />
== Tutorials, Software Links, and Other Relevant Class Information==<br />
*[http://ringo.ams.sunysb.edu/index.php/Rizzo_Lab_Information_and_Tutorials Rizzo_Lab_Information_and_Tutorials]<br />
*Cheat Sheet: <br />
**[[Unix]] <br />
**[[Vi]] <br />
**[[BASH scripting]] <br />
**[[C_Shell_Scripting]] <br />
**[[SLURM]]<br />
*[http://www.ee.surrey.ac.uk/Teaching/Unix/index.html Unix Command Guide]<br />
*[https://it.stonybrook.edu/help/kb/seawulf-queues Seawulf Queue Info]<br />
*[https://en.wikipedia.org/wiki/Help:Cheatsheet Wikitext Cheat Sheet (for preparing tutorial Wiki page)]<br />
*[https://www.mediawiki.org/wiki/Help:Formatting Wikitext Formatting Tips (for making the tutorial Wiki page pretty)]<br />
*[https://www.youtube.com/watch?v=hQxKYSUdiD8 Chimera Basics - Video]<br />
*[https://www.youtube.com/watch?v=eLxhKc7Ljjk Chimera Structure Analysis - Video]<br />
*[https://njardarson.lab.arizona.edu/content/top-pharmaceuticals-poster Top Pharmaceutical Posters]<br />
*[http://dock.compbio.ucsf.edu/DOCK_6/dock6_manual.htm DOCK6.9 User Manual]<br />
*[http://ambermd.org/doc12/Amber16.pdf AMBER 16 User Manual]<br />
*[http://www.alchemistry.org/wiki/Main_Page Free Energy Calculations]<br />
<br />
== Schedule ==<br />
* Please note that a doctor's excuse will be required if you miss your scheduled oral presentation date because of illness.<br />
<br />
<br />
{| align="center" border="1" cellpadding="8" cellspacing="0" style="background:white; text-align:left; width:95%"<br />
|- style="background:lightblue"<br />
| '''Date'''<br />
| '''Participant'''<br />
| '''Notes'''<br />
|-<br />
| || '''SECTION 1: COMPUTING INFRASTRUCTURE AND TOOLS''' ||<br />
|-<br />
| 2020.01.27 Mon || Group Study || '''First Day of Class''' <br> Seawulf accounts setup <br> unix / vim / csh introduction <br> Discuss presentations and final projects (OHARE sheets)<br />
|-<br />
| 2020.01.29 Wed || Group Study || Seawulf accounts setup <br> unix / vim / csh introduction <br> Visualization demo's Chimera and VMD<br />
|-<br />
| 2020.02.03 Mon ||| Group Study || Seawulf accounts setup <br> unix / vim / csh introduction <br> Visualization demo's Chimera and VMD<br />
|-<br />
| 2020.02.05 Wed ||| Group Study || Seawulf accounts setup <br> unix / vim / csh introduction <br> Visualization demo's Chimera and VMD<br />
|-<br />
| 2020.02.10 Mon || Group Study || Seawulf queuing system <br> <br />
|-<br />
| 2020.02.12 Wed || Group Study || Seawulf queuing system <br> Ethics in Writing (Rob)<br />
|-<br />
| || '''SECTION 2: DOCK TUTORIAL''' || [http://ringo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2013.02.18.ams536.pdf see Joe Allen DOCK slides] <br />
|-<br />
| 2020.02.17 Mon || Group Study || '''Draft Student Project Proposal OHARE Sheet Due''' <br> Tutorials: DOCK virtual screening <br> individual project discussion <br />
|-<br />
| 2020.02.19 Wed || Group Study || Tutorials: DOCK virtual screening <br> individual project discussion<br />
|-<br />
| 2020.02.24 Mon || Group Study || '''Final Student Project Proposal OHARE Sheet Due''' <br> Tutorials: DOCK virtual screening <br> individual project discussion<br />
|-<br />
| 2020.02.26 Wed || Group Study || Tutorials: DOCK virtual screening <br> individual project discussion<br />
|-<br />
| 2020.03.02 Mon || Group Study || Tutorials: DOCK virtual screening <br> individual project discussion<br />
|-<br />
| 2020.03.04 Wed || Group Study || Tutorials: DOCK virtual screening <br> individual project discussion<br />
|-<br />
| 2020.03.09 Mon || Group Study || Tutorials: DOCK de novo design <br> individual project discussion<br />
|-<br />
| 2020.03.11 Wed || Group Study || Tutorials: DOCK de novo design <br> individual project discussion <br />
|-<br />
| 2020.03.16 Mon || '''Spring Recess''' || '''Spring Recess'''<br />
|-<br />
| 2020.03.18 Wed || '''Spring Recess''' || '''Spring Recess'''<br />
|-<br />
| || '''REVISED SCHEDULE BEGINS HERE''' || '''REVISED SCHEDULE BEGINS HERE''' <br />
|-<br />
| 2020.03.23 Mon || '''Extended Spring Recess''' || '''Extended Spring Recess''' <br> Please make sure that the Zoom program is up and running on your home computer <br> https://it.stonybrook.edu/services/zoom<br />
|-<br />
| 2020.03.25 Wed || '''Extended Spring Recess''' || '''Extended Spring Recess''' <br> Please make sure that the Zoom program is up and running on your home computer <br> https://it.stonybrook.edu/services/zoom<br />
|-<br />
| || '''SECTION 3: AMBER TUTORIAL''' || [http://ringo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2012.02.29.ams536.lingling.amber_intro.pdf see Lingling Jiang AMBER slides ] <br> [http://ringo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/AMS536_contingency_plan.pdf see Steve Telehaney slides]<br />
|-<br />
| 2020.03.30 Mon || Online Group Study || Tutorials: AMBER molecular dynamics <br> [http://ringo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/001_amber.mov see AMBER Video #1 ] <br> individual project discussion<br />
|-<br />
| 2020.04.01 Wed || Online Group Study || Tutorials: AMBER molecular dynamics <br> [http://ringo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/002_amber_tleap.mp4 see AMBER Video #2.1 ] <br> [http://ringo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/002_amber_visualize.mov see AMBER Video #2.2 ] <br> [http://ringo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/002_amber_equilibration.mov see AMBER Video #2.3 ] <br> individual project discussion<br />
|-<br />
| 2020.04.06 Mon || Online Group Study || Tutorials: AMBER molecular dynamics <br> [http://ringo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/003_amber_production_intro.mov see AMBER Video #3.1 ] <br> [http://ringo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/003_amber.mov see AMBER Video #3.2 ] <br> individual project discussion<br />
|-<br />
| 2020.04.08 Wed || Online Group Study || Tutorials: AMBER molecular dynamics <br> [http://ringo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/004_amber.mov see AMBER Video #4.1 ] <br> [http://ringo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/004_amber_part2.mov see AMBER Video #4.2 ] <br>[http://ringo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/004_amber_plot1.mov see AMBER Video #4.3 ] <br> individual project discussion<br />
|-<br />
| 2020.04.13 Mon || Online Group Study || Tutorials: AMBER molecular dynamics <br> [http://ringo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/005_amber.mov see AMBER Video #5 ] <br> individual project discussion<br />
|- <br />
| 2020.04.15 Wed || Online Group Study || Tutorials: AMBER molecular dynamics <br> [http://ringo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/006_amber.mov see AMBER Video #6 ] <br> individual project discussion<br />
|-<br />
| || '''SECTION 4: CLASS PROJECTS''' ||<br />
|-<br />
| 2020.04.20 Mon || Online Group Study || '''Draft Paper Due''' <br> Project Analysis/Troubleshooting <br />
|-<br />
| 2020.04.22 Wed || Online Group Study || Project Analysis/Troubleshooting <br />
|-<br />
| 2020.04.27 Mon || Online Group Study || '''Video Presentations of Class Projects Must be Emailed to Guilherme by 2:30PM (please name files as "Lastname.mp4")'''<br> Project Analysis/Troubleshooting <br> <br> Each course participant will watch and evaluate 3 Presentations (~ 20 minutes each) based on the Reviewer Assignment schedule below and submit a [http://ringo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2020_ams.536.presentation.assessment.docx Presentation Assessment Sheet] for each Video (due 1 week from today). Instructors will evaluate 3-4 presentations each. <br />
<br><br />
'''(1) [http://ringo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/videos/Corbo.mp4 Corbo]'''<br />
*Guerra<br />
*Zhu<br />
*Stepanenko<br />
<br />
'''(2) [http://ringo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/videos/Guerra.mp4 Guerra]'''<br />
*Chakraborti<br />
*Zhang<br />
*Pak<br />
<br />
'''(3) [http://ringo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/videos/Laverty.mp4 Laverty]'''<br />
*Jayanetti<br />
*Cardetti<br />
*Guerra<br />
<br />
'''(4) [http://ringo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/videos/Jayanetti.mp4 Jayanetti]'''<br />
*He<br />
*Corbo<br />
*Pak<br />
<br />
'''(5) [http://ringo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/videos/Stepanenko.mov Stepanenko]'''<br />
*He<br />
*Cardetti<br />
*Zhu<br />
<br />
'''(6) [http://ringo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/videos/Zhang.mp4 Zhang]'''<br />
*Chakraborti<br />
*Corbo<br />
*Laverty<br />
<br />
'''(7) [http://ringo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/videos/Chakraborti.mp4 Chakraborti]'''<br />
*Guerra<br />
*Pak<br />
*Zhu<br />
<br />
'''(8) [http://ringo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/videos/Pak.mp4 Pak]'''<br />
*He<br />
*Laverty<br />
*Cardetti<br />
<br />
'''(9) [http://ringo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/videos/Cardetti.mp4 Cardetti]'''<br />
*Zhang<br />
*Corbo<br />
*Jayanetti<br />
<br />
'''(10) [http://ringo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/videos/Zhu.mp4 Zhu]'''<br />
*Zhang<br />
*Stepanenko<br />
*Jayanetti<br />
<br />
'''(11) [http://ringo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/videos/He.mp4 He]'''<br />
*Stepanenko<br />
*Chakraborti<br />
*Laverty<br />
<br />
'''(12) Rob'''<br />
*Corbo<br />
*Guerra<br />
*Laverty<br />
*Jayanetti<br />
<br />
'''(13) Steve'''<br />
*Stepanenko<br />
*Zhang<br />
*Chakraborti<br />
*Pak<br />
<br />
'''(14) Guilherme'''<br />
*Cardetti<br />
*Zhu<br />
*He<br />
<br />
<br />
|-<br />
| 2020.04.29 Wed || Online Group Study || Project Analysis/Troubleshooting <br />
|-<br />
| 2020.05.04 Mon || Online Group Study || '''[http://ringo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2020_ams.536.presentation.assessment.docx Presentation Assessment Sheets] Must Be Emailed to Guilherme by 2:30PM based on your Reviewer Assignments from above''' <br> Project Analysis/Troubleshooting<br />
|-<br />
| 2020.05.06 Wed || Online Group Study || '''Last Day Class'''<br> Project Analysis/Troubleshooting<br />
|-<br />
| 2020.05.08 Fri || '''Final Written Report due by 5PM today.''' || '''Final Written Report due by 5PM today.''' <br> Please email electronic copy to rizzorc -at- gmail dot com and guilherme dot duarteramosmatos -at- stonybrook dot edu<br />
|-<br />
|}<br />
<br><br />
<br><br />
'''GENERAL INFORMATION:''' AMS-536 is designed for students who wish to gain hands-on experience modeling biological molecules at the atomic level. In conjunction with the participants' interest, Molecular Mechanics, molecular dynamics, Monte Carlo, Docking (virtual screening), or Quantum Mechanics software packages will be used. Projects will include setup, execution, and analysis. Students will work on individual projects outside of class. Course participants will give presentations relevant to the simulations being performed and a final project report will be required. Grades will be based on the quality of the talks, participation in class discussion, attendance, and the final written report. Familiarity with working in a Unix (Linux) environment is desirable.<br />
<br />
<br />
'''Learning Obectives:'''<br />
*(1) Gain hands-on experience modeling biological molecules at the atomic level. <br />
*(2) Learn to navigate linx/unix operating system <br />
*(3) Learn shell scripting and text-based editing (vim program)<br />
*(4) Learn to use a linux-based computing cluster that has a queuing system<br />
*(5) Learn to use visualization software (Chimera, MOE, and VMD programs)<br />
*(6) Setup, execute, and analyze docking (DOCK) and molecular dynamics (AMBER) tutorials. <br />
*(7) Give oral presentations on individual research projects which includes:<br />
**(i) Introduction/Background (include biological relevance)<br />
**(ii) Specifics of Your System<br />
**(iii) Computational Details (theory)<br />
**(iv) Computational Details (system setup)<br />
**(v) Results and Discussion (include a critical interpretation of your results)<br />
**(vi) Conclusions<br />
**(vii) Future<br />
**(viii) Acknowledgments<br />
*(8) Write a polished well-referenced manuscript in the format of a peer-reviewed Journal Article.<br />
<br />
<br />
<br />
'''LITERATURE DISCLAIMER:''' Hyperlinks and manuscripts accessed through Stony Brook University's electronic journal subscriptions are provided below for educational purposes only.<br />
<br />
<br />
'''PRESENTATION DISCLAIMER:''' Presentations may contain slides from a variety of online sources for educational and illustrative purposes only, and use here does not imply that the presenter is claiming that the contents are their own original work or research.<br />
<br />
<br />
'''Required Syllabi Statements:''' The University Senate has authorized that the following required statements appear in all teaching syllabi on the Stony Brook Campus. This information is also located on the Provostâ€™s website: https://www.stonybrook.edu/commcms/provost/faculty/handbook/academic_policies/syllabus_statement.php<br />
<br />
<br />
'''Student Accessibility Support Center Statement:''' If you have a physical, psychological, medical, or learning disability that may impact your course work, please contact the Student Accessibility Support Center, 128 ECC Building, (631) 632-6748, or at sasc@stonybrook.edu. They will determine with you what accommodations are necessary and appropriate. All information and documentation is confidential.<br />
<br />
Students who require assistance during emergency evacuation are encouraged to discuss their needs with their professors and the Student Accessibility Support Center. For procedures and information go to the following website: https://ehs.stonybrook.edu/programs/fire-safety/emergency-evacuation/evacuation-guide-people-physical-disabilities and search Fire Safety and Evacuation and Disabilities. <br />
<br />
*To access mental health services, call Counseling and Psychological Services at 631-632-6720; Counselors are available to speak with 24/7.<br />
<br />
*For updated information on the Academic Success and Tutoring Center please check www.stonybrook.edu/tutoring for the most up-to-date information.<br />
<br />
*For IT Support: Students can visit the Keep Learning website at https://sites.google.com/stonybrook.edu/keeplearning for information on the tools you need for alternative and online learning. Need help? Report technical issues at https://it.stonybrook.edu/services/itsm or call 631-632-2358.<br />
<br />
*For information on Library services and resources please visit the Continuity of Library Operations guide.<br />
<br />
<br />
'''Faculty Technical Support Statement:''' <br />
*Faculty needing to access information on using instructional technology for remote teaching should visit https://it.stonybrook.edu/keep-teaching<br />
*If you experience problems using technology, please submit a service ticket at: https://it.stonybrook.edu/services/itsm<br />
*CELT will provide remote support by Zoom at: https://stonybrook.zoom.us/j/478142498 or by email at: academictechnologies@stonybrook.edu<br />
<br />
<br />
'''Academic Integrity Statement:''' Each student must pursue his or her academic goals honestly and be personally accountable for all submitted work. Representing another person's work as your own is always wrong. Faculty is required to report any suspected instances of academic dishonesty to the Academic Judiciary. Faculty in the Health Sciences Center (School of Health Technology & Management, Nursing, Social Welfare, Dental Medicine) and School of Medicine are required to follow their school-specific procedures. For more comprehensive information on academic integrity, including categories of academic dishonesty please refer to the academic judiciary website at http://www.stonybrook.edu/commcms/academic_integrity/index.html<br />
<br />
<br />
'''Critical Incident Management:''' Stony Brook University expects students to respect the rights, privileges, and property of other people. Faculty are required to report to the Office of University Community Standards any disruptive behavior that interrupts their ability to teach, compromises the safety of the learning environment, or inhibits students' ability to learn. Faculty in the HSC Schools and the School of Medicine are required to follow their school-specific procedures. Further information about most academic matters can be found in the Undergraduate Bulletin, the Undergraduate Class Schedule, and the Faculty-Employee Handbook.</div>Lprentishttps://ringo.ams.stonybrook.edu/index.php?title=DOCK_Abbreviations_Guide&diff=13105DOCK Abbreviations Guide2020-04-15T14:57:56Z<p>Lprentis: </p>
<hr />
<div>This is a DOCK abbreviations guide for the language used in the user manual and online tutorials.<br />
<br />
* AG = Anchor and Grow<br />
* CD = Covalent De Novo<br />
* CV = Covalent Attach and Grow<br />
* DN = De Novo<br />
* GA = Genetic Algorithm<br />
* VS = Virtual Screen<br />
* ES = Electrostatic <br />
* VDW = Van der Waals<br />
* DCE = DOCK Cartesian Energy/Continuous Score<br />
* FMS = Pharmacophore Matching Similarity<br />
* FPS = Footprint Matching Similarity<br />
* HMS = Hungarian Matching Similarity<br />
* MGE = Multigrid Energy Score<br />
* MGS = Multigrid Score (MGE +FPS)<br />
* VOS = Volume Overlap Similarity</div>Lprentishttps://ringo.ams.stonybrook.edu/index.php?title=Scoring_Functions&diff=13104Scoring Functions2020-04-15T14:57:14Z<p>Lprentis: /* Pharmacophore Matching Similarity Score */</p>
<hr />
<div>DOCK uses several types of scoring functions to discriminate among orientations and molecules. Scoring is requested using the score_molecules parameter. A large portion of scoring functions can be called through descriptor score (but not all). Those with descriptor score functionality will be denoted in bold. <br />
<br />
== Continuous/DOCK Cartesian Energy Score==<br />
Continuous scoring may be used to evaluate a ligand:receptor complex without the investment of a grid calculation, or to perform a more detailed calculation without the numerical approximation of the grid. '''Continuous score is implemented under Descriptor Score as well'''. Continuous score is a cartesian based score and can be combined with other Cartesian based scores with very little computational expense.<br />
<br />
===Continuous/DCE Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
|continuous_score_primary<br />
| Does the user want to perform continuous non-grid scoring as the primary scoring function?<br />
| no<br />
|-<br />
|continuous_score_secondary <br />
| Does the user want to perform continuous non-grid scoring as the secondary scoring function? <br />
|no<br />
|-<br />
|cont_score_rec_filename <br />
|File that contains receptor coordinates <br />
|receptor.mol2<br />
|-<br />
|cont_score_att_exp <br />
|VDW Lennard-Jones potential attractive exponent <br />
|6<br />
|-<br />
|cont_score_rep_exp <br />
|VDW Lennard-Jones potential repulsive exponent <br />
|12<br />
|-<br />
|cont_score_rep_rad_scale <br />
|Scalar multiplier of the radii for the repulsive portion of the vdw energy component only <br />
|1.0<br />
|-<br />
|cont_score_use_dist_dep_dielectric <br />
|Distance dependent dielectric switch <br />
|yes<br />
|-<br />
|cont_score_dielectric <br />
|Dielectric constant for the electrostatic term <br />
|<br />
|- <br />
|cont_score_vdw_scale <br />
|Scalar multiplier of vdw energy component <br />
|1 <br />
|-<br />
|cont_score_vdw_scale <br />
|Flag to turn off vdw portion of the scoring function when cont_score_vdw_scale=0 <br />
|yes<br />
|- <br />
|cont_score_es_scale <br />
|Scalar multiplier of electrostatic energy component <br />
|1.0 <br />
|-<br />
|cont_score_turn_off_es <br />
|Flag to turn off es portion of the scoring function when cont_score_es_scale = 0 <br />
|yes<br />
|-<br />
|}<br />
<br />
===Continuous/DCE Score Output Components===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
|Continuous_score<br />
|sum of the van der Waals and electrostatic interactions<br />
|-<br />
|Continuous_vdw_energy<br />
|VDW interaction between ligand and receptor<br />
|-<br />
|Continuous_es_energy<br />
|ES interaction between the ligand and receptor<br />
|-<br />
|}<br />
<br />
==Grid-Based Score== <br />
DOCK needs a fast scoring function to evaluate poses rapidly during growth. The energy grid is used for this. The grid stores the non-bonded Molecular Mechanics Potential of the receptor at each grid point. <br />
[[Image:Mm-equation.png|center]]<br />
'''Grid can be called under descriptor score but it is suggested to not mix grid-based and cartesian space as that will dramatically increase computing time.'''<br />
===Grid Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
| grid_score_primary<br />
| Does the user want to perform grid-based energy scoring as the primary scoring function? || yes- <br />
|-<br />
| grid_score_rep_rad_scale<br />
| Scalar multiplier of the radii for the repulsive portion of the VDW energy component only when grid score is turned on || 1.0<br />
|-<br />
| grid_score_vdw_scale <br />
| Scalar multiplier of the VDW energy component || 1<br />
|-<br />
| grid_score_turn_off_vdw <br />
| A flag to turn off vdw portion of scoring function when grid score vdw scale = 0 || yes<br />
|-<br />
| grid_score_es_scale <br />
| Flag to scale up or down the es portion of the scoring function when es scale is turned on || 1<br />
|-<br />
| grid_score_turn_off_es <br />
| A flag to turn off es portion of scoring function when grid score es scale = 0 || yes<br />
|-<br />
| grid_score_grid_prefix <br />
| The prefix to the grid files containing the desired nrg/bmp grid || grid<br />
|-<br />
|}<br />
<br />
===Grid Score Output Components===<br />
These values will be printed in the header of the mol2 file post DOCK process.<br />
<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
| Grid_score<br />
| Sum of the VDW and ES interactions <br />
|-<br />
| Grid_vdw_energy<br />
| VDW interaction between the ligand grid<br />
|-<br />
| Grid_es_energy<br />
| ES interaction betweent eh ligand and grid<br />
|}<br />
<br />
==MultiGrid Score== <br />
The MultiGrid Score is similar to the Footprint Score described below, except that in the case of the Multi-Grid Score, the pair-wise interaction energies are computed over multiple grids rather than in Cartesian space. This is done to improve the tractability of FPS calculations as well as to make it simple to combine FPS and standard Grid Score. If the multiple grids are prepared as recommended than the sum of the interactions with each grid should equal the interaction of a standard DOCK grid representing the entire target. By default MultiGrid score will equal the sum of the interactions with all grids plus a FPS component generated by treating each grid as a protein residue. User defined scaling factors allow MultiGrid score to be set to equal Grid score, FPS score or any combination thereof. Generally, "important" receptor residues are identified before-hand based on the magnitude of their interaction with the reference ligand, then a unique grid is generated to represent each of those residues. Finally, a "remainder" grid is generated to represent all remaining receptor residues. The scoring function itself will then calculate intermolecular VDW and ES energies for the reference ligand and pose ligand on each of the grids (also called footprints), then it will calculate the footprint similarity using either the Standard Euclidean, Normalized Euclidean, or Pearson Correlation similarity metrics.<br />
<br />
'''MultiGrid can be called under descriptor score but it is suggested to not mix grid-based and cartesian space as that will dramatically increase computing time.'''<br />
<br />
===MultiGrid Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
| multigrid_score_primary<br />
| Does the user want to perform grid-based energy scoring as the primary scoring function? || yes- <br />
|-<br />
| multigrid_score_rep_rad_scale<br />
| Scalar multiplier of the radii for the repulsive portion of the VDW energy component only when grid score is turned on || 1.0<br />
|-<br />
| multigrid_score_vdw_scale <br />
| Scalar multiplier of the VDW energy component || 1<br />
|-<br />
| multigrid_score_es_scale <br />
| Flag to scale up or down the es portion of the scoring function when es scale is turned on || 1<br />
|-<br />
|multigrid_score_number_of_grids <br />
|Path to the reference txt file - only used when footprint reference txt is turned on. <br />
|ligand_footprint.txt<br />
|-<br />
|multigrid_score_grid_prefix0 <br />
|Provide prefixes to identify the grids. Note that the first grid starts at '0'. The last grid should be the remainder grid. This must be done for each grid. <br />
|multigrid0<br />
|-<br />
|multigrid_score_individual_rec_ensemble <br />
|Flag for individual receptor (standard) or multiple receptor (not implemented yet). <br />
|no<br />
|-<br />
|multigrid_score_weights_text <br />
|Flag for providing a textfile as input for the reference footprint. <br />
|no<br />
|-<br />
|multigrid_score_footprint_text <br />
|Name of the reference footprint input text file, when multigrid_score_weight_text is turned on. <br />
|reference.txt<br />
|-<br />
|multigrid_score_fp_ref_mol <br />
|Flag for providing a MOL2 as input for the reference footprint. <br />
|no<br />
|-<br />
|multigrid_score_footprint_ref <br />
|Name of the reference footprint input MOL2 file, when multigrid_score_fp_ref_mol is turned on. <br />
|reference.mol2<br />
|-<br />
|multigrid_score_foot_compare_type <br />
|Footprint similarity calculation methods (Options: Euclidean, Pearson). If Pearson, the correlation coefficient as the metric to compare the footprints. When the value is 1 then there is perfect agreement between the two footprints. WHen the value is 0 then there is poor agreement between the two footprints. If Euclidean, the Euclidean distance as the metric to compare the footprints. When the value is 0 then there is perfect agreement btween the two footprints. As the agreement gets worse between the two footprints the value increases. <br />
|Euclidean<br />
|-<br />
|multigrid_score_normalize_foot <br />
|normalization is used only with Euclidean distance. <br />
|no<br />
|-<br />
|multigrid_score_vdw_euc_scale <br />
|Scaling factor for VDW term. when using euclidean <br />
|1.0<br />
|-<br />
|multigrid_score_es_euc_scale <br />
|Scaling factor for ES term when using euclidean <br />
|1.0<br />
|-<br />
|multigrid_score_vdw_norm_scale <br />
|Scaling factor for VDW term. euclidean and normalize <br />
|10.0<br />
|-<br />
|multigrid_score_es_norm_scale <br />
|Scaling factor for ES term. Flags if using Pearson Correlation similarity metric for footprint comparison. <br />
|10.0<br />
|-<br />
|multigrid_score_vdw_cor_scale <br />
|Scaling factor for VDW term <br />
|(-10.0)<br />
|-<br />
|multigrid_score_es_cor_scale <br />
|Scaling factor for ES term <br />
|(-10.0)<br />
|-<br />
|}<br />
<br />
===MultiGrid Score Output Components===<br />
These values will be printed in the header of the mol2 file post DOCK process.<br />
<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
| MultiGrid_score<br />
| Sum of the VDW and ES interactions <br />
|-<br />
| MultiGrid_vdw_energy<br />
| VDW interaction between the ligand grid<br />
|-<br />
| MultiGrid_es_energy<br />
| ES interaction betweent eh ligand and grid<br />
|-<br />
| MGS_vdw+es_energy<br />
|sum of VDW and ES components<br />
|-<br />
|MGS_vdw_fps<br />
|VDW footprint similarity score<br />
|-<br />
|MGS_es_fps<br />
|ES footprint similarity score<br />
|-<br />
|MGS_vdw+es_fps<br />
|sum of VDW adn ES footprint similarity scores<br />
|-<br />
|}<br />
<br />
==Footprint Similarity Score==<br />
The Footprint Similarity Score is a scoring function that calculates intermolecular hydrogen bonds and footprint comparisons, in addition to standard intermolecular energies (VDW and ES). <br />
<br />
Intermolecular Energies (VDW, ES) are calculated the same way as in Continuous Score.<br />
<br />
A geometric definition of Hydrogen bonds is employed. We define 3 atoms XD, HD, and XA as the heavy atom donor, donated hydrogen, and heavy atom acceptor, respectively. There is a hydrogen bond present if the following two conditions are met:<br />
<br />
# The distance between HD and XA is less than or equal to 2.5 angstroms;<br />
# The angle defined by XD, HD, and XA is between 120 and 180 degrees.<br />
<br />
Footprints are a per-residue decomposition of interactions between the ligand and the receptor. This can be performed for all three terms VDW, ES, HB.<br />
Two footprints can be compared in three ways: Standard Euclidean, Normalized Euclidean, Pearson Correlation.<br />
<br />
Footprints are used to gauge how similar two poses or two molecules are to one-another. For applications to virtual screening applications a reference is required.<br />
<br />
There are to choices for a reference:<br />
<br />
# One can give a mol2 file containing a reference molecule, and footprints will be calculated.<br />
# One can pass a text file containing VDW, ES, and H-bond footprints. <br />
There are different choices for selection of residues:<br />
<br />
# All residues.<br />
# Residues chosen using a threshold (union of the sets of reference and pose). The VDW, ES, and HB footprints may have different residues chosen in this case.<br />
# Selected residues.<br />
<br />
Note that for (2) and (3) the remaining residue interaction may be placed in a remainder value included in the footprint.<br />
<br />
'''Footprint Similarity Score can be called under Descriptor Score.'''<br />
<br />
===Footprint Similarity Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
|footprint_similarity_score_primary <br />
|Flag to perform footprint scoring as the primary scoring function <br />
|no<br />
|-<br />
|footprint_similarity_score_secondary <br />
|Flag to perform footprint scoring as the secondary scoring function. <br />
|no<br />
|-<br />
|fps_score_use_footprint_reference_mol2 <br />
|Use a molecule to calculate footprint reference. <br />
|no<br />
|-<br />
|fps_score_footprint_reference_mol2_filename <br />
|Path to the reference mol2 file - only used when footprint reference mol2 is turned on. <br />
|ligand_footprint.mol2<br />
|-<br />
|fps_score_use_footprint_reference_txt <br />
|Use a pre-calculated footprint reference in text format. <br />
|no<br />
|-<br />
|fps_score_footprint_reference_txt_filename <br />
|Path to the reference txt file - only used when footprint reference txt is turned on. <br />
|ligand_footprint.txt<br />
|-<br />
|fps_score_foot_compare_type <br />
|Footprint similarity calculation methods (Options: Euclidean, Pearson). If Pearson, the correlation coefficient as the metric to compare the footprints. When the value is 1 then there is perfect agreement between the two footprints. WHen the value is 0 then there is poor agreement between the two footprints. If Euclidean, the Euclidean distance as the metric to compare the footprints. When the value is 0 then there is perfect agreement btween the two footprints. As the agreement gets worse between the two footprints the value increases. <br />
|Euclidean<br />
|-<br />
|fps_score_normalize_foot <br />
|normalization is used only with Euclidean distance. <br />
|no<br />
|-<br />
|fps_score_foot_comp_all_residue <br />
|If yes all residues are used for calculating the footprint. <br />
|yes<br />
|-<br />
|fps_score_choose_foot_range_type <br />
|User can use to determine the type of the range of the footprint by either specifying a residue range or defining a threshold. If specify_range, the user chooses to use a residue range and all footprints will be evaluated only on this residue range. First residue id = 1 not 0. If threshold, the user chose to use a residue range that is defined by only residues that have magnitudes that exceed the specified thresholds. (Options: specify_range, threshold) <br />
|specify_range<br />
|-<br />
|fps_score_vdw_threshold <br />
|Specify threshold for van der Waals energy, when threshold is turned on. <br />
|1<br />
|-<br />
|fps_score_es_threshold <br />
|Specify threshold for electrostatic energy, when threshold is turned on. <br />
|1<br />
|-<br />
|fps_score_hb_threshold <br />
|specify threshold for hydrogen bonds (integers). 0.5 means that all none zeros are used, when threshold is turned on. <br />
|0.5<br />
|-<br />
|fps_score_use_remainder <br />
|Interaction remainder is all remaining residues not included individually <br />
|yes<br />
|-<br />
|fps_score_rec_filename <br />
|File that contains receptor coordinates <br />
|receptor.mol2<br />
|-<br />
|fps_score_att_exp <br />
|VDW Lennard-Jones potential attractive exponent <br />
|6<br />
|-<br />
|fps_score_rep_exp <br />
|VDW Lennard-Jones potential repulsive exponent <br />
|12<br />
|-<br />
|fps_score_rep_rad_scale <br />
|Scalar multiplier of the radii for the repulsive portion of the VDW energy component ONLY <br />
|1<br />
|-<br />
|fps_score_use_distance_dependent_dielectric <br />
|Distance dependent dielectric switch <br />
|yes<br />
|-<br />
|fps_score_dielectric <br />
|Dielectric constant for electrostatic term <br />
|4.0<br />
|-<br />
|fps_score_vdw_scale <br />
|Scalar multiplier of vdw energy component <br />
|1<br />
|-<br />
|fps_score_es_scale <br />
|Scalar multiplier of es energy component <br />
|1<br />
|-<br />
|fps_score_hb_scale <br />
|Scalar multiplier of hb energy component <br />
|0<br />
|-<br />
|fps_score_internal_scale <br />
|Scalar multiplier of internal energy component <br />
|0<br />
|-<br />
|fps_score_fp_vwd_scale <br />
|Scalar multiplier of vdw footprint component <br />
|0<br />
|-<br />
|fps_score_fp_es_scale <br />
|Scalar multiplier of es footprint component <br />
|0<br />
|-<br />
|fps_score_fp_hb_scale <br />
|Scalar multiplier of hb footprint component <br />
|0<br />
|-<br />
|}<br />
<br />
===Footprint Similarity Score Output Components===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
|Footprint_similarity_score<br />
|sum of the van der Waals, electostatic, and hbond footprint similarity scores<br />
|-<br />
|FPS_vdw_energy<br />
|VDW interaction between ligand and receptor<br />
|-<br />
|FPS_es_energy<br />
|ES interaction between the ligand and receptor<br />
|-<br />
|FPS_num_hbond<br />
|number of hydrogen bonds<br />
|-<br />
|FPS_vdw+es_energy<br />
|sum of the van der Waals and electrostatic components<br />
|-<br />
|FPS_vdw_fps<br />
|vdw footprint similarity score<br />
|-<br />
|FPS_es_fps<br />
|ES footprint similarity score<br />
|-<br />
|FPS_hb_fps<br />
|hbond footprint similarity score<br />
|-<br />
|FPS_vdw_fp_numres<br />
|number of residues in the receptor considered during the calculation<br />
|-<br />
|FPS_es_fp_numres<br />
|number of residues in the receptor considered during the calculation<br />
|-<br />
|FPS_hb_fp_numres<br />
|number of residues in the receptor considered during the calculation<br />
|-<br />
|}<br />
<br />
==Pharmacophore Matching Similarity Score==<br />
The Pharmacophore Matching Similarity score is a scoring function that calculates the level of pharmacophore overlap between a reference molecule and a candidate molecule in three dimensional space.The functional form for quantifying the pharmacophore overlap in a virtual screening experiment using DOCK, termed pharmacophore matching similarity (FMS), is as follows:<br />
[[File:fms_equation.jpg|center]]<br />
<br />
'''Pharmacophore Matching Similarity Score can be called under Descriptor Score.''' <br />
<br />
===Pharmacophore Matching Similarity Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
|pharmacophore_score_primary <br />
|Flag to perform FMS scoring as the primary scoring function <br />
|no<br />
|-<br />
|fms_score_use_ref_mol2 <br />
|Use a molecule to calculate pharmacophore reference <br />
|no<br />
|-<br />
|fms_score_ref_mol2_filename <br />
|molecule reference input file name. <br />
|Ph4.mol2<br />
|-<br />
|fms_score_use_ref_txt <br />
|Use a text format pharmacophore reference. <br />
|no<br />
|-<br />
|fms_score_ref_txt_filename <br />
|text reference input file name. <br />
|Ph4.txt<br />
|-<br />
|fms_score_write_reference_pharmacophore_mol2 <br />
|Flag to write the reference pharmacophore model as a mol2 output file. <br />
|no<br />
|-<br />
|fms_score_write_reference_ph4_txt <br />
|Flag to write the reference pharmacophore model as a txt output file. <br />
|no<br />
|-<br />
|fms_score_reference_output_mol2_filename <br />
|reference pharmacophore mol2 output file name. <br />
|ref_ph4.mol2<br />
|-<br />
|fms_score_reference_output_txt_filename <br />
|Reference pharmacophore txt output file name. <br />
|ref_ph4.txt<br />
|-<br />
|fms_score_write_candidate_pharmacophore <br />
|Flag to write the candidate pharmacophore model as a mol2 output file.<br />
| no<br />
|-<br />
|fms_score_candidate_output_filename <br />
|Candidate pharmacophore output file name <br />
|cad_ph4.mol2<br />
|-<br />
|fms_score_write_matched_pharmacophore<br />
| Flag to write the matched pharmacophore model as a mol2 output file. The matched pharmacophore model, which is consist of pharmacophore points well-matched to any reference pharmacophore point, is a subset of the candidate pharmacophore model. <br />
|no<br />
|-<br />
|fms_score_matched_output_filename <br />
|matched pharmacophore output file name. <br />
|mat_ph4.mol2<br />
|-<br />
|fms_score_compare_type <br />
|Flag to determine comparison method between reference and candidate ph4. If overlap user is using a ligand-based reference for computing the FMS. When the value is 0 then there is a perfect overlap. When the value is negative then you have multi-matched ph4. When the value is positive then you have matches with residual. If compatible (This is under development and not currently available) user is using a receptor based reference for computing the FMS. When the value is X then there is a perfect overlap. When the value is Y then you have multi-matched ph4. When the value is Z then you have matches with residual.(Options: overlap, compatible) <br />
|overlap<br />
|-<br />
|fms_score_full_match <br />
|Flag to determine if full match is desired. Currently only full match is considered. <br />
|yes<br />
|-<br />
|fms_score_match_rate_weight <br />
|Specify the constant parameter k (weight on the match rate term) in FMS score <br />
|5<br />
|-<br />
|fms_score_match_proj_cutoff <br />
|Specify the scalar projection cutoff Ïƒ in the pharmacophore matching protocol. Default value cos(45 ï¿½ ) â‰ˆ 0.7071 corresponds to a vector angle cutoff of 45 ï¿½ <br />
|0.7071<br />
|-<br />
|fms_score_max_score <br />
|Specify the FMS score value for pharmacophore model pairs with no matches. This maximum FMS score depends on k, r and Ïƒ. <br />
|20<br />
|-<br />
|}</div>Lprentishttps://ringo.ams.stonybrook.edu/index.php?title=Scoring_Functions&diff=13103Scoring Functions2020-04-14T18:42:56Z<p>Lprentis: /* Pharmacophore Matching Similarity Score Parameters */</p>
<hr />
<div>DOCK uses several types of scoring functions to discriminate among orientations and molecules. Scoring is requested using the score_molecules parameter. A large portion of scoring functions can be called through descriptor score (but not all). Those with descriptor score functionality will be denoted in bold. <br />
<br />
== Continuous/DOCK Cartesian Energy Score==<br />
Continuous scoring may be used to evaluate a ligand:receptor complex without the investment of a grid calculation, or to perform a more detailed calculation without the numerical approximation of the grid. '''Continuous score is implemented under Descriptor Score as well'''. Continuous score is a cartesian based score and can be combined with other Cartesian based scores with very little computational expense.<br />
<br />
===Continuous/DCE Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
|continuous_score_primary<br />
| Does the user want to perform continuous non-grid scoring as the primary scoring function?<br />
| no<br />
|-<br />
|continuous_score_secondary <br />
| Does the user want to perform continuous non-grid scoring as the secondary scoring function? <br />
|no<br />
|-<br />
|cont_score_rec_filename <br />
|File that contains receptor coordinates <br />
|receptor.mol2<br />
|-<br />
|cont_score_att_exp <br />
|VDW Lennard-Jones potential attractive exponent <br />
|6<br />
|-<br />
|cont_score_rep_exp <br />
|VDW Lennard-Jones potential repulsive exponent <br />
|12<br />
|-<br />
|cont_score_rep_rad_scale <br />
|Scalar multiplier of the radii for the repulsive portion of the vdw energy component only <br />
|1.0<br />
|-<br />
|cont_score_use_dist_dep_dielectric <br />
|Distance dependent dielectric switch <br />
|yes<br />
|-<br />
|cont_score_dielectric <br />
|Dielectric constant for the electrostatic term <br />
|<br />
|- <br />
|cont_score_vdw_scale <br />
|Scalar multiplier of vdw energy component <br />
|1 <br />
|-<br />
|cont_score_vdw_scale <br />
|Flag to turn off vdw portion of the scoring function when cont_score_vdw_scale=0 <br />
|yes<br />
|- <br />
|cont_score_es_scale <br />
|Scalar multiplier of electrostatic energy component <br />
|1.0 <br />
|-<br />
|cont_score_turn_off_es <br />
|Flag to turn off es portion of the scoring function when cont_score_es_scale = 0 <br />
|yes<br />
|-<br />
|}<br />
<br />
===Continuous/DCE Score Output Components===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
|Continuous_score<br />
|sum of the van der Waals and electrostatic interactions<br />
|-<br />
|Continuous_vdw_energy<br />
|VDW interaction between ligand and receptor<br />
|-<br />
|Continuous_es_energy<br />
|ES interaction between the ligand and receptor<br />
|-<br />
|}<br />
<br />
==Grid-Based Score== <br />
DOCK needs a fast scoring function to evaluate poses rapidly during growth. The energy grid is used for this. The grid stores the non-bonded Molecular Mechanics Potential of the receptor at each grid point. <br />
[[Image:Mm-equation.png|center]]<br />
'''Grid can be called under descriptor score but it is suggested to not mix grid-based and cartesian space as that will dramatically increase computing time.'''<br />
===Grid Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
| grid_score_primary<br />
| Does the user want to perform grid-based energy scoring as the primary scoring function? || yes- <br />
|-<br />
| grid_score_rep_rad_scale<br />
| Scalar multiplier of the radii for the repulsive portion of the VDW energy component only when grid score is turned on || 1.0<br />
|-<br />
| grid_score_vdw_scale <br />
| Scalar multiplier of the VDW energy component || 1<br />
|-<br />
| grid_score_turn_off_vdw <br />
| A flag to turn off vdw portion of scoring function when grid score vdw scale = 0 || yes<br />
|-<br />
| grid_score_es_scale <br />
| Flag to scale up or down the es portion of the scoring function when es scale is turned on || 1<br />
|-<br />
| grid_score_turn_off_es <br />
| A flag to turn off es portion of scoring function when grid score es scale = 0 || yes<br />
|-<br />
| grid_score_grid_prefix <br />
| The prefix to the grid files containing the desired nrg/bmp grid || grid<br />
|-<br />
|}<br />
<br />
===Grid Score Output Components===<br />
These values will be printed in the header of the mol2 file post DOCK process.<br />
<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
| Grid_score<br />
| Sum of the VDW and ES interactions <br />
|-<br />
| Grid_vdw_energy<br />
| VDW interaction between the ligand grid<br />
|-<br />
| Grid_es_energy<br />
| ES interaction betweent eh ligand and grid<br />
|}<br />
<br />
==MultiGrid Score== <br />
The MultiGrid Score is similar to the Footprint Score described below, except that in the case of the Multi-Grid Score, the pair-wise interaction energies are computed over multiple grids rather than in Cartesian space. This is done to improve the tractability of FPS calculations as well as to make it simple to combine FPS and standard Grid Score. If the multiple grids are prepared as recommended than the sum of the interactions with each grid should equal the interaction of a standard DOCK grid representing the entire target. By default MultiGrid score will equal the sum of the interactions with all grids plus a FPS component generated by treating each grid as a protein residue. User defined scaling factors allow MultiGrid score to be set to equal Grid score, FPS score or any combination thereof. Generally, "important" receptor residues are identified before-hand based on the magnitude of their interaction with the reference ligand, then a unique grid is generated to represent each of those residues. Finally, a "remainder" grid is generated to represent all remaining receptor residues. The scoring function itself will then calculate intermolecular VDW and ES energies for the reference ligand and pose ligand on each of the grids (also called footprints), then it will calculate the footprint similarity using either the Standard Euclidean, Normalized Euclidean, or Pearson Correlation similarity metrics.<br />
<br />
'''MultiGrid can be called under descriptor score but it is suggested to not mix grid-based and cartesian space as that will dramatically increase computing time.'''<br />
<br />
===MultiGrid Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
| multigrid_score_primary<br />
| Does the user want to perform grid-based energy scoring as the primary scoring function? || yes- <br />
|-<br />
| multigrid_score_rep_rad_scale<br />
| Scalar multiplier of the radii for the repulsive portion of the VDW energy component only when grid score is turned on || 1.0<br />
|-<br />
| multigrid_score_vdw_scale <br />
| Scalar multiplier of the VDW energy component || 1<br />
|-<br />
| multigrid_score_es_scale <br />
| Flag to scale up or down the es portion of the scoring function when es scale is turned on || 1<br />
|-<br />
|multigrid_score_number_of_grids <br />
|Path to the reference txt file - only used when footprint reference txt is turned on. <br />
|ligand_footprint.txt<br />
|-<br />
|multigrid_score_grid_prefix0 <br />
|Provide prefixes to identify the grids. Note that the first grid starts at '0'. The last grid should be the remainder grid. This must be done for each grid. <br />
|multigrid0<br />
|-<br />
|multigrid_score_individual_rec_ensemble <br />
|Flag for individual receptor (standard) or multiple receptor (not implemented yet). <br />
|no<br />
|-<br />
|multigrid_score_weights_text <br />
|Flag for providing a textfile as input for the reference footprint. <br />
|no<br />
|-<br />
|multigrid_score_footprint_text <br />
|Name of the reference footprint input text file, when multigrid_score_weight_text is turned on. <br />
|reference.txt<br />
|-<br />
|multigrid_score_fp_ref_mol <br />
|Flag for providing a MOL2 as input for the reference footprint. <br />
|no<br />
|-<br />
|multigrid_score_footprint_ref <br />
|Name of the reference footprint input MOL2 file, when multigrid_score_fp_ref_mol is turned on. <br />
|reference.mol2<br />
|-<br />
|multigrid_score_foot_compare_type <br />
|Footprint similarity calculation methods (Options: Euclidean, Pearson). If Pearson, the correlation coefficient as the metric to compare the footprints. When the value is 1 then there is perfect agreement between the two footprints. WHen the value is 0 then there is poor agreement between the two footprints. If Euclidean, the Euclidean distance as the metric to compare the footprints. When the value is 0 then there is perfect agreement btween the two footprints. As the agreement gets worse between the two footprints the value increases. <br />
|Euclidean<br />
|-<br />
|multigrid_score_normalize_foot <br />
|normalization is used only with Euclidean distance. <br />
|no<br />
|-<br />
|multigrid_score_vdw_euc_scale <br />
|Scaling factor for VDW term. when using euclidean <br />
|1.0<br />
|-<br />
|multigrid_score_es_euc_scale <br />
|Scaling factor for ES term when using euclidean <br />
|1.0<br />
|-<br />
|multigrid_score_vdw_norm_scale <br />
|Scaling factor for VDW term. euclidean and normalize <br />
|10.0<br />
|-<br />
|multigrid_score_es_norm_scale <br />
|Scaling factor for ES term. Flags if using Pearson Correlation similarity metric for footprint comparison. <br />
|10.0<br />
|-<br />
|multigrid_score_vdw_cor_scale <br />
|Scaling factor for VDW term <br />
|(-10.0)<br />
|-<br />
|multigrid_score_es_cor_scale <br />
|Scaling factor for ES term <br />
|(-10.0)<br />
|-<br />
|}<br />
<br />
===MultiGrid Score Output Components===<br />
These values will be printed in the header of the mol2 file post DOCK process.<br />
<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
| MultiGrid_score<br />
| Sum of the VDW and ES interactions <br />
|-<br />
| MultiGrid_vdw_energy<br />
| VDW interaction between the ligand grid<br />
|-<br />
| MultiGrid_es_energy<br />
| ES interaction betweent eh ligand and grid<br />
|-<br />
| MGS_vdw+es_energy<br />
|sum of VDW and ES components<br />
|-<br />
|MGS_vdw_fps<br />
|VDW footprint similarity score<br />
|-<br />
|MGS_es_fps<br />
|ES footprint similarity score<br />
|-<br />
|MGS_vdw+es_fps<br />
|sum of VDW adn ES footprint similarity scores<br />
|-<br />
|}<br />
<br />
==Footprint Similarity Score==<br />
The Footprint Similarity Score is a scoring function that calculates intermolecular hydrogen bonds and footprint comparisons, in addition to standard intermolecular energies (VDW and ES). <br />
<br />
Intermolecular Energies (VDW, ES) are calculated the same way as in Continuous Score.<br />
<br />
A geometric definition of Hydrogen bonds is employed. We define 3 atoms XD, HD, and XA as the heavy atom donor, donated hydrogen, and heavy atom acceptor, respectively. There is a hydrogen bond present if the following two conditions are met:<br />
<br />
# The distance between HD and XA is less than or equal to 2.5 angstroms;<br />
# The angle defined by XD, HD, and XA is between 120 and 180 degrees.<br />
<br />
Footprints are a per-residue decomposition of interactions between the ligand and the receptor. This can be performed for all three terms VDW, ES, HB.<br />
Two footprints can be compared in three ways: Standard Euclidean, Normalized Euclidean, Pearson Correlation.<br />
<br />
Footprints are used to gauge how similar two poses or two molecules are to one-another. For applications to virtual screening applications a reference is required.<br />
<br />
There are to choices for a reference:<br />
<br />
# One can give a mol2 file containing a reference molecule, and footprints will be calculated.<br />
# One can pass a text file containing VDW, ES, and H-bond footprints. <br />
There are different choices for selection of residues:<br />
<br />
# All residues.<br />
# Residues chosen using a threshold (union of the sets of reference and pose). The VDW, ES, and HB footprints may have different residues chosen in this case.<br />
# Selected residues.<br />
<br />
Note that for (2) and (3) the remaining residue interaction may be placed in a remainder value included in the footprint.<br />
<br />
'''Footprint Similarity Score can be called under Descriptor Score.'''<br />
<br />
===Footprint Similarity Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
|footprint_similarity_score_primary <br />
|Flag to perform footprint scoring as the primary scoring function <br />
|no<br />
|-<br />
|footprint_similarity_score_secondary <br />
|Flag to perform footprint scoring as the secondary scoring function. <br />
|no<br />
|-<br />
|fps_score_use_footprint_reference_mol2 <br />
|Use a molecule to calculate footprint reference. <br />
|no<br />
|-<br />
|fps_score_footprint_reference_mol2_filename <br />
|Path to the reference mol2 file - only used when footprint reference mol2 is turned on. <br />
|ligand_footprint.mol2<br />
|-<br />
|fps_score_use_footprint_reference_txt <br />
|Use a pre-calculated footprint reference in text format. <br />
|no<br />
|-<br />
|fps_score_footprint_reference_txt_filename <br />
|Path to the reference txt file - only used when footprint reference txt is turned on. <br />
|ligand_footprint.txt<br />
|-<br />
|fps_score_foot_compare_type <br />
|Footprint similarity calculation methods (Options: Euclidean, Pearson). If Pearson, the correlation coefficient as the metric to compare the footprints. When the value is 1 then there is perfect agreement between the two footprints. WHen the value is 0 then there is poor agreement between the two footprints. If Euclidean, the Euclidean distance as the metric to compare the footprints. When the value is 0 then there is perfect agreement btween the two footprints. As the agreement gets worse between the two footprints the value increases. <br />
|Euclidean<br />
|-<br />
|fps_score_normalize_foot <br />
|normalization is used only with Euclidean distance. <br />
|no<br />
|-<br />
|fps_score_foot_comp_all_residue <br />
|If yes all residues are used for calculating the footprint. <br />
|yes<br />
|-<br />
|fps_score_choose_foot_range_type <br />
|User can use to determine the type of the range of the footprint by either specifying a residue range or defining a threshold. If specify_range, the user chooses to use a residue range and all footprints will be evaluated only on this residue range. First residue id = 1 not 0. If threshold, the user chose to use a residue range that is defined by only residues that have magnitudes that exceed the specified thresholds. (Options: specify_range, threshold) <br />
|specify_range<br />
|-<br />
|fps_score_vdw_threshold <br />
|Specify threshold for van der Waals energy, when threshold is turned on. <br />
|1<br />
|-<br />
|fps_score_es_threshold <br />
|Specify threshold for electrostatic energy, when threshold is turned on. <br />
|1<br />
|-<br />
|fps_score_hb_threshold <br />
|specify threshold for hydrogen bonds (integers). 0.5 means that all none zeros are used, when threshold is turned on. <br />
|0.5<br />
|-<br />
|fps_score_use_remainder <br />
|Interaction remainder is all remaining residues not included individually <br />
|yes<br />
|-<br />
|fps_score_rec_filename <br />
|File that contains receptor coordinates <br />
|receptor.mol2<br />
|-<br />
|fps_score_att_exp <br />
|VDW Lennard-Jones potential attractive exponent <br />
|6<br />
|-<br />
|fps_score_rep_exp <br />
|VDW Lennard-Jones potential repulsive exponent <br />
|12<br />
|-<br />
|fps_score_rep_rad_scale <br />
|Scalar multiplier of the radii for the repulsive portion of the VDW energy component ONLY <br />
|1<br />
|-<br />
|fps_score_use_distance_dependent_dielectric <br />
|Distance dependent dielectric switch <br />
|yes<br />
|-<br />
|fps_score_dielectric <br />
|Dielectric constant for electrostatic term <br />
|4.0<br />
|-<br />
|fps_score_vdw_scale <br />
|Scalar multiplier of vdw energy component <br />
|1<br />
|-<br />
|fps_score_es_scale <br />
|Scalar multiplier of es energy component <br />
|1<br />
|-<br />
|fps_score_hb_scale <br />
|Scalar multiplier of hb energy component <br />
|0<br />
|-<br />
|fps_score_internal_scale <br />
|Scalar multiplier of internal energy component <br />
|0<br />
|-<br />
|fps_score_fp_vwd_scale <br />
|Scalar multiplier of vdw footprint component <br />
|0<br />
|-<br />
|fps_score_fp_es_scale <br />
|Scalar multiplier of es footprint component <br />
|0<br />
|-<br />
|fps_score_fp_hb_scale <br />
|Scalar multiplier of hb footprint component <br />
|0<br />
|-<br />
|}<br />
<br />
===Footprint Similarity Score Output Components===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
|Footprint_similarity_score<br />
|sum of the van der Waals, electostatic, and hbond footprint similarity scores<br />
|-<br />
|FPS_vdw_energy<br />
|VDW interaction between ligand and receptor<br />
|-<br />
|FPS_es_energy<br />
|ES interaction between the ligand and receptor<br />
|-<br />
|FPS_num_hbond<br />
|number of hydrogen bonds<br />
|-<br />
|FPS_vdw+es_energy<br />
|sum of the van der Waals and electrostatic components<br />
|-<br />
|FPS_vdw_fps<br />
|vdw footprint similarity score<br />
|-<br />
|FPS_es_fps<br />
|ES footprint similarity score<br />
|-<br />
|FPS_hb_fps<br />
|hbond footprint similarity score<br />
|-<br />
|FPS_vdw_fp_numres<br />
|number of residues in the receptor considered during the calculation<br />
|-<br />
|FPS_es_fp_numres<br />
|number of residues in the receptor considered during the calculation<br />
|-<br />
|FPS_hb_fp_numres<br />
|number of residues in the receptor considered during the calculation<br />
|-<br />
|}<br />
<br />
==Pharmacophore Matching Similarity Score==<br />
The Pharmacophore Matching Similarity score is a scoring function that calculates the level of pharmacophore overlap between a reference molecule and a candidate molecule in three dimensional space.The functional form for quantifying the pharmacophore overlap in a virtual screening experiment using DOCK, termed pharmacophore matching similarity (FMS), is as follows:<br />
[[File:fms_equation.jpg]]<br />
<br />
'''Pharmacophore Matching Similarity Score can be called under Descriptor Score.''' <br />
<br />
===Pharmacophore Matching Similarity Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
|pharmacophore_score_primary <br />
|Flag to perform FMS scoring as the primary scoring function <br />
|no<br />
|-<br />
|fms_score_use_ref_mol2 <br />
|Use a molecule to calculate pharmacophore reference <br />
|no<br />
|-<br />
|fms_score_ref_mol2_filename <br />
|molecule reference input file name. <br />
|Ph4.mol2<br />
|-<br />
|fms_score_use_ref_txt <br />
|Use a text format pharmacophore reference. <br />
|no<br />
|-<br />
|fms_score_ref_txt_filename <br />
|text reference input file name. <br />
|Ph4.txt<br />
|-<br />
|fms_score_write_reference_pharmacophore_mol2 <br />
|Flag to write the reference pharmacophore model as a mol2 output file. <br />
|no<br />
|-<br />
|fms_score_write_reference_ph4_txt <br />
|Flag to write the reference pharmacophore model as a txt output file. <br />
|no<br />
|-<br />
|fms_score_reference_output_mol2_filename <br />
|reference pharmacophore mol2 output file name. <br />
|ref_ph4.mol2<br />
|-<br />
|fms_score_reference_output_txt_filename <br />
|Reference pharmacophore txt output file name. <br />
|ref_ph4.txt<br />
|-<br />
|fms_score_write_candidate_pharmacophore <br />
|Flag to write the candidate pharmacophore model as a mol2 output file.<br />
| no<br />
|-<br />
|fms_score_candidate_output_filename <br />
|Candidate pharmacophore output file name <br />
|cad_ph4.mol2<br />
|-<br />
|fms_score_write_matched_pharmacophore<br />
| Flag to write the matched pharmacophore model as a mol2 output file. The matched pharmacophore model, which is consist of pharmacophore points well-matched to any reference pharmacophore point, is a subset of the candidate pharmacophore model. <br />
|no<br />
|-<br />
|fms_score_matched_output_filename <br />
|matched pharmacophore output file name. <br />
|mat_ph4.mol2<br />
|-<br />
|fms_score_compare_type <br />
|Flag to determine comparison method between reference and candidate ph4. If overlap user is using a ligand-based reference for computing the FMS. When the value is 0 then there is a perfect overlap. When the value is negative then you have multi-matched ph4. When the value is positive then you have matches with residual. If compatible (This is under development and not currently available) user is using a receptor based reference for computing the FMS. When the value is X then there is a perfect overlap. When the value is Y then you have multi-matched ph4. When the value is Z then you have matches with residual.(Options: overlap, compatible) <br />
|overlap<br />
|-<br />
|fms_score_full_match <br />
|Flag to determine if full match is desired. Currently only full match is considered. <br />
|yes<br />
|-<br />
|fms_score_match_rate_weight <br />
|Specify the constant parameter k (weight on the match rate term) in FMS score <br />
|5<br />
|-<br />
|fms_score_match_proj_cutoff <br />
|Specify the scalar projection cutoff Ïƒ in the pharmacophore matching protocol. Default value cos(45 ï¿½ ) â‰ˆ 0.7071 corresponds to a vector angle cutoff of 45 ï¿½ <br />
|0.7071<br />
|-<br />
|fms_score_max_score <br />
|Specify the FMS score value for pharmacophore model pairs with no matches. This maximum FMS score depends on k, r and Ïƒ. <br />
|20<br />
|-<br />
|}</div>Lprentishttps://ringo.ams.stonybrook.edu/index.php?title=Scoring_Functions&diff=13102Scoring Functions2020-04-14T18:40:54Z<p>Lprentis: /* Pharmacophore Matching Similarity Score */</p>
<hr />
<div>DOCK uses several types of scoring functions to discriminate among orientations and molecules. Scoring is requested using the score_molecules parameter. A large portion of scoring functions can be called through descriptor score (but not all). Those with descriptor score functionality will be denoted in bold. <br />
<br />
== Continuous/DOCK Cartesian Energy Score==<br />
Continuous scoring may be used to evaluate a ligand:receptor complex without the investment of a grid calculation, or to perform a more detailed calculation without the numerical approximation of the grid. '''Continuous score is implemented under Descriptor Score as well'''. Continuous score is a cartesian based score and can be combined with other Cartesian based scores with very little computational expense.<br />
<br />
===Continuous/DCE Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
|continuous_score_primary<br />
| Does the user want to perform continuous non-grid scoring as the primary scoring function?<br />
| no<br />
|-<br />
|continuous_score_secondary <br />
| Does the user want to perform continuous non-grid scoring as the secondary scoring function? <br />
|no<br />
|-<br />
|cont_score_rec_filename <br />
|File that contains receptor coordinates <br />
|receptor.mol2<br />
|-<br />
|cont_score_att_exp <br />
|VDW Lennard-Jones potential attractive exponent <br />
|6<br />
|-<br />
|cont_score_rep_exp <br />
|VDW Lennard-Jones potential repulsive exponent <br />
|12<br />
|-<br />
|cont_score_rep_rad_scale <br />
|Scalar multiplier of the radii for the repulsive portion of the vdw energy component only <br />
|1.0<br />
|-<br />
|cont_score_use_dist_dep_dielectric <br />
|Distance dependent dielectric switch <br />
|yes<br />
|-<br />
|cont_score_dielectric <br />
|Dielectric constant for the electrostatic term <br />
|<br />
|- <br />
|cont_score_vdw_scale <br />
|Scalar multiplier of vdw energy component <br />
|1 <br />
|-<br />
|cont_score_vdw_scale <br />
|Flag to turn off vdw portion of the scoring function when cont_score_vdw_scale=0 <br />
|yes<br />
|- <br />
|cont_score_es_scale <br />
|Scalar multiplier of electrostatic energy component <br />
|1.0 <br />
|-<br />
|cont_score_turn_off_es <br />
|Flag to turn off es portion of the scoring function when cont_score_es_scale = 0 <br />
|yes<br />
|-<br />
|}<br />
<br />
===Continuous/DCE Score Output Components===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
|Continuous_score<br />
|sum of the van der Waals and electrostatic interactions<br />
|-<br />
|Continuous_vdw_energy<br />
|VDW interaction between ligand and receptor<br />
|-<br />
|Continuous_es_energy<br />
|ES interaction between the ligand and receptor<br />
|-<br />
|}<br />
<br />
==Grid-Based Score== <br />
DOCK needs a fast scoring function to evaluate poses rapidly during growth. The energy grid is used for this. The grid stores the non-bonded Molecular Mechanics Potential of the receptor at each grid point. <br />
[[Image:Mm-equation.png|center]]<br />
'''Grid can be called under descriptor score but it is suggested to not mix grid-based and cartesian space as that will dramatically increase computing time.'''<br />
===Grid Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
| grid_score_primary<br />
| Does the user want to perform grid-based energy scoring as the primary scoring function? || yes- <br />
|-<br />
| grid_score_rep_rad_scale<br />
| Scalar multiplier of the radii for the repulsive portion of the VDW energy component only when grid score is turned on || 1.0<br />
|-<br />
| grid_score_vdw_scale <br />
| Scalar multiplier of the VDW energy component || 1<br />
|-<br />
| grid_score_turn_off_vdw <br />
| A flag to turn off vdw portion of scoring function when grid score vdw scale = 0 || yes<br />
|-<br />
| grid_score_es_scale <br />
| Flag to scale up or down the es portion of the scoring function when es scale is turned on || 1<br />
|-<br />
| grid_score_turn_off_es <br />
| A flag to turn off es portion of scoring function when grid score es scale = 0 || yes<br />
|-<br />
| grid_score_grid_prefix <br />
| The prefix to the grid files containing the desired nrg/bmp grid || grid<br />
|-<br />
|}<br />
<br />
===Grid Score Output Components===<br />
These values will be printed in the header of the mol2 file post DOCK process.<br />
<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
| Grid_score<br />
| Sum of the VDW and ES interactions <br />
|-<br />
| Grid_vdw_energy<br />
| VDW interaction between the ligand grid<br />
|-<br />
| Grid_es_energy<br />
| ES interaction betweent eh ligand and grid<br />
|}<br />
<br />
==MultiGrid Score== <br />
The MultiGrid Score is similar to the Footprint Score described below, except that in the case of the Multi-Grid Score, the pair-wise interaction energies are computed over multiple grids rather than in Cartesian space. This is done to improve the tractability of FPS calculations as well as to make it simple to combine FPS and standard Grid Score. If the multiple grids are prepared as recommended than the sum of the interactions with each grid should equal the interaction of a standard DOCK grid representing the entire target. By default MultiGrid score will equal the sum of the interactions with all grids plus a FPS component generated by treating each grid as a protein residue. User defined scaling factors allow MultiGrid score to be set to equal Grid score, FPS score or any combination thereof. Generally, "important" receptor residues are identified before-hand based on the magnitude of their interaction with the reference ligand, then a unique grid is generated to represent each of those residues. Finally, a "remainder" grid is generated to represent all remaining receptor residues. The scoring function itself will then calculate intermolecular VDW and ES energies for the reference ligand and pose ligand on each of the grids (also called footprints), then it will calculate the footprint similarity using either the Standard Euclidean, Normalized Euclidean, or Pearson Correlation similarity metrics.<br />
<br />
'''MultiGrid can be called under descriptor score but it is suggested to not mix grid-based and cartesian space as that will dramatically increase computing time.'''<br />
<br />
===MultiGrid Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
| multigrid_score_primary<br />
| Does the user want to perform grid-based energy scoring as the primary scoring function? || yes- <br />
|-<br />
| multigrid_score_rep_rad_scale<br />
| Scalar multiplier of the radii for the repulsive portion of the VDW energy component only when grid score is turned on || 1.0<br />
|-<br />
| multigrid_score_vdw_scale <br />
| Scalar multiplier of the VDW energy component || 1<br />
|-<br />
| multigrid_score_es_scale <br />
| Flag to scale up or down the es portion of the scoring function when es scale is turned on || 1<br />
|-<br />
|multigrid_score_number_of_grids <br />
|Path to the reference txt file - only used when footprint reference txt is turned on. <br />
|ligand_footprint.txt<br />
|-<br />
|multigrid_score_grid_prefix0 <br />
|Provide prefixes to identify the grids. Note that the first grid starts at '0'. The last grid should be the remainder grid. This must be done for each grid. <br />
|multigrid0<br />
|-<br />
|multigrid_score_individual_rec_ensemble <br />
|Flag for individual receptor (standard) or multiple receptor (not implemented yet). <br />
|no<br />
|-<br />
|multigrid_score_weights_text <br />
|Flag for providing a textfile as input for the reference footprint. <br />
|no<br />
|-<br />
|multigrid_score_footprint_text <br />
|Name of the reference footprint input text file, when multigrid_score_weight_text is turned on. <br />
|reference.txt<br />
|-<br />
|multigrid_score_fp_ref_mol <br />
|Flag for providing a MOL2 as input for the reference footprint. <br />
|no<br />
|-<br />
|multigrid_score_footprint_ref <br />
|Name of the reference footprint input MOL2 file, when multigrid_score_fp_ref_mol is turned on. <br />
|reference.mol2<br />
|-<br />
|multigrid_score_foot_compare_type <br />
|Footprint similarity calculation methods (Options: Euclidean, Pearson). If Pearson, the correlation coefficient as the metric to compare the footprints. When the value is 1 then there is perfect agreement between the two footprints. WHen the value is 0 then there is poor agreement between the two footprints. If Euclidean, the Euclidean distance as the metric to compare the footprints. When the value is 0 then there is perfect agreement btween the two footprints. As the agreement gets worse between the two footprints the value increases. <br />
|Euclidean<br />
|-<br />
|multigrid_score_normalize_foot <br />
|normalization is used only with Euclidean distance. <br />
|no<br />
|-<br />
|multigrid_score_vdw_euc_scale <br />
|Scaling factor for VDW term. when using euclidean <br />
|1.0<br />
|-<br />
|multigrid_score_es_euc_scale <br />
|Scaling factor for ES term when using euclidean <br />
|1.0<br />
|-<br />
|multigrid_score_vdw_norm_scale <br />
|Scaling factor for VDW term. euclidean and normalize <br />
|10.0<br />
|-<br />
|multigrid_score_es_norm_scale <br />
|Scaling factor for ES term. Flags if using Pearson Correlation similarity metric for footprint comparison. <br />
|10.0<br />
|-<br />
|multigrid_score_vdw_cor_scale <br />
|Scaling factor for VDW term <br />
|(-10.0)<br />
|-<br />
|multigrid_score_es_cor_scale <br />
|Scaling factor for ES term <br />
|(-10.0)<br />
|-<br />
|}<br />
<br />
===MultiGrid Score Output Components===<br />
These values will be printed in the header of the mol2 file post DOCK process.<br />
<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
| MultiGrid_score<br />
| Sum of the VDW and ES interactions <br />
|-<br />
| MultiGrid_vdw_energy<br />
| VDW interaction between the ligand grid<br />
|-<br />
| MultiGrid_es_energy<br />
| ES interaction betweent eh ligand and grid<br />
|-<br />
| MGS_vdw+es_energy<br />
|sum of VDW and ES components<br />
|-<br />
|MGS_vdw_fps<br />
|VDW footprint similarity score<br />
|-<br />
|MGS_es_fps<br />
|ES footprint similarity score<br />
|-<br />
|MGS_vdw+es_fps<br />
|sum of VDW adn ES footprint similarity scores<br />
|-<br />
|}<br />
<br />
==Footprint Similarity Score==<br />
The Footprint Similarity Score is a scoring function that calculates intermolecular hydrogen bonds and footprint comparisons, in addition to standard intermolecular energies (VDW and ES). <br />
<br />
Intermolecular Energies (VDW, ES) are calculated the same way as in Continuous Score.<br />
<br />
A geometric definition of Hydrogen bonds is employed. We define 3 atoms XD, HD, and XA as the heavy atom donor, donated hydrogen, and heavy atom acceptor, respectively. There is a hydrogen bond present if the following two conditions are met:<br />
<br />
# The distance between HD and XA is less than or equal to 2.5 angstroms;<br />
# The angle defined by XD, HD, and XA is between 120 and 180 degrees.<br />
<br />
Footprints are a per-residue decomposition of interactions between the ligand and the receptor. This can be performed for all three terms VDW, ES, HB.<br />
Two footprints can be compared in three ways: Standard Euclidean, Normalized Euclidean, Pearson Correlation.<br />
<br />
Footprints are used to gauge how similar two poses or two molecules are to one-another. For applications to virtual screening applications a reference is required.<br />
<br />
There are to choices for a reference:<br />
<br />
# One can give a mol2 file containing a reference molecule, and footprints will be calculated.<br />
# One can pass a text file containing VDW, ES, and H-bond footprints. <br />
There are different choices for selection of residues:<br />
<br />
# All residues.<br />
# Residues chosen using a threshold (union of the sets of reference and pose). The VDW, ES, and HB footprints may have different residues chosen in this case.<br />
# Selected residues.<br />
<br />
Note that for (2) and (3) the remaining residue interaction may be placed in a remainder value included in the footprint.<br />
<br />
'''Footprint Similarity Score can be called under Descriptor Score.'''<br />
<br />
===Footprint Similarity Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
|footprint_similarity_score_primary <br />
|Flag to perform footprint scoring as the primary scoring function <br />
|no<br />
|-<br />
|footprint_similarity_score_secondary <br />
|Flag to perform footprint scoring as the secondary scoring function. <br />
|no<br />
|-<br />
|fps_score_use_footprint_reference_mol2 <br />
|Use a molecule to calculate footprint reference. <br />
|no<br />
|-<br />
|fps_score_footprint_reference_mol2_filename <br />
|Path to the reference mol2 file - only used when footprint reference mol2 is turned on. <br />
|ligand_footprint.mol2<br />
|-<br />
|fps_score_use_footprint_reference_txt <br />
|Use a pre-calculated footprint reference in text format. <br />
|no<br />
|-<br />
|fps_score_footprint_reference_txt_filename <br />
|Path to the reference txt file - only used when footprint reference txt is turned on. <br />
|ligand_footprint.txt<br />
|-<br />
|fps_score_foot_compare_type <br />
|Footprint similarity calculation methods (Options: Euclidean, Pearson). If Pearson, the correlation coefficient as the metric to compare the footprints. When the value is 1 then there is perfect agreement between the two footprints. WHen the value is 0 then there is poor agreement between the two footprints. If Euclidean, the Euclidean distance as the metric to compare the footprints. When the value is 0 then there is perfect agreement btween the two footprints. As the agreement gets worse between the two footprints the value increases. <br />
|Euclidean<br />
|-<br />
|fps_score_normalize_foot <br />
|normalization is used only with Euclidean distance. <br />
|no<br />
|-<br />
|fps_score_foot_comp_all_residue <br />
|If yes all residues are used for calculating the footprint. <br />
|yes<br />
|-<br />
|fps_score_choose_foot_range_type <br />
|User can use to determine the type of the range of the footprint by either specifying a residue range or defining a threshold. If specify_range, the user chooses to use a residue range and all footprints will be evaluated only on this residue range. First residue id = 1 not 0. If threshold, the user chose to use a residue range that is defined by only residues that have magnitudes that exceed the specified thresholds. (Options: specify_range, threshold) <br />
|specify_range<br />
|-<br />
|fps_score_vdw_threshold <br />
|Specify threshold for van der Waals energy, when threshold is turned on. <br />
|1<br />
|-<br />
|fps_score_es_threshold <br />
|Specify threshold for electrostatic energy, when threshold is turned on. <br />
|1<br />
|-<br />
|fps_score_hb_threshold <br />
|specify threshold for hydrogen bonds (integers). 0.5 means that all none zeros are used, when threshold is turned on. <br />
|0.5<br />
|-<br />
|fps_score_use_remainder <br />
|Interaction remainder is all remaining residues not included individually <br />
|yes<br />
|-<br />
|fps_score_rec_filename <br />
|File that contains receptor coordinates <br />
|receptor.mol2<br />
|-<br />
|fps_score_att_exp <br />
|VDW Lennard-Jones potential attractive exponent <br />
|6<br />
|-<br />
|fps_score_rep_exp <br />
|VDW Lennard-Jones potential repulsive exponent <br />
|12<br />
|-<br />
|fps_score_rep_rad_scale <br />
|Scalar multiplier of the radii for the repulsive portion of the VDW energy component ONLY <br />
|1<br />
|-<br />
|fps_score_use_distance_dependent_dielectric <br />
|Distance dependent dielectric switch <br />
|yes<br />
|-<br />
|fps_score_dielectric <br />
|Dielectric constant for electrostatic term <br />
|4.0<br />
|-<br />
|fps_score_vdw_scale <br />
|Scalar multiplier of vdw energy component <br />
|1<br />
|-<br />
|fps_score_es_scale <br />
|Scalar multiplier of es energy component <br />
|1<br />
|-<br />
|fps_score_hb_scale <br />
|Scalar multiplier of hb energy component <br />
|0<br />
|-<br />
|fps_score_internal_scale <br />
|Scalar multiplier of internal energy component <br />
|0<br />
|-<br />
|fps_score_fp_vwd_scale <br />
|Scalar multiplier of vdw footprint component <br />
|0<br />
|-<br />
|fps_score_fp_es_scale <br />
|Scalar multiplier of es footprint component <br />
|0<br />
|-<br />
|fps_score_fp_hb_scale <br />
|Scalar multiplier of hb footprint component <br />
|0<br />
|-<br />
|}<br />
<br />
===Footprint Similarity Score Output Components===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
|Footprint_similarity_score<br />
|sum of the van der Waals, electostatic, and hbond footprint similarity scores<br />
|-<br />
|FPS_vdw_energy<br />
|VDW interaction between ligand and receptor<br />
|-<br />
|FPS_es_energy<br />
|ES interaction between the ligand and receptor<br />
|-<br />
|FPS_num_hbond<br />
|number of hydrogen bonds<br />
|-<br />
|FPS_vdw+es_energy<br />
|sum of the van der Waals and electrostatic components<br />
|-<br />
|FPS_vdw_fps<br />
|vdw footprint similarity score<br />
|-<br />
|FPS_es_fps<br />
|ES footprint similarity score<br />
|-<br />
|FPS_hb_fps<br />
|hbond footprint similarity score<br />
|-<br />
|FPS_vdw_fp_numres<br />
|number of residues in the receptor considered during the calculation<br />
|-<br />
|FPS_es_fp_numres<br />
|number of residues in the receptor considered during the calculation<br />
|-<br />
|FPS_hb_fp_numres<br />
|number of residues in the receptor considered during the calculation<br />
|-<br />
|}<br />
<br />
==Pharmacophore Matching Similarity Score==<br />
The Pharmacophore Matching Similarity score is a scoring function that calculates the level of pharmacophore overlap between a reference molecule and a candidate molecule in three dimensional space.The functional form for quantifying the pharmacophore overlap in a virtual screening experiment using DOCK, termed pharmacophore matching similarity (FMS), is as follows:<br />
[[File:fms_equation.jpg]]<br />
<br />
'''Pharmacophore Matching Similarity Score can be called under Descriptor Score.''' <br />
<br />
===Pharmacophore Matching Similarity Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
|pharmacophore_score_primary <br />
|Flag to perform FMS scoring as the primary scoring function <br />
|no<br />
|-<br />
|fms_score_use_ref_mol2 <br />
|Use a molecule to calculate pharmacophore reference <br />
|no<br />
|-<br />
|fms_score_ref_mol2_filename <br />
|molecule reference input file name. <br />
|Ph4.mol2<br />
|-<br />
|fms_score_use_ref_txt <br />
|Use a text format pharmacophore reference. <br />
|no<br />
|-<br />
|fms_score_ref_txt_filename <br />
|text reference input file name. <br />
|Ph4.txt<br />
|-<br />
|fms_score_write_reference_pharmacophore_mol2 <br />
|Flag to write the reference pharmacophore model as a mol2 output file. <br />
|no<br />
|-<br />
|fms_score_write_reference_ph4_txt <br />
|Flag to write the reference pharmacophore model as a txt output file. <br />
|no<br />
|-<br />
|fms_score_reference_output_mol2_filename <br />
|reference pharmacophore mol2 output file name. <br />
|ref_ph4.mol2<br />
|-<br />
|fms_score_reference_output_txt_filename <br />
|Reference pharmacophore txt output file name. <br />
|ref_ph4.txt<br />
|-<br />
|fms_score_write_candidate_pharmacophore <br />
|Flag to write the candidate pharmacophore model as a mol2 output file.<br />
| no<br />
|-<br />
fms_score_candidate_output_filename Candidate pharmacophore output file name cad_ph4.mol2<br />
fms_score_write_matched_pharmacophore Flag to write the matched pharmacophore model as a mol2 output file. The matched pharmacophore model, which is consist of pharmacophore points well-matched to any reference pharmacophore point, is a subset of the candidate pharmacophore model. no<br />
fms_score_matched_output_filename matched pharmacophore output file name. mat_ph4.mol2<br />
fms_score_compare_type Flag to determine comparison method between reference and candidate ph4. If overlap user is using a ligand-based reference for computing the FMS. When the value is 0 then there is a perfect overlap. When the value is negative then you have multi-matched ph4. When the value is positive then you have matches with residual. If compatible (This is under development and not currently available) user is using a receptor based reference for computing the FMS. When the value is X then there is a perfect overlap. When the value is Y then you have multi-matched ph4. When the value is Z then you have matches with residual.(Options: overlap, compatible) overlap<br />
fms_score_full_match Flag to determine if full match is desired. Currently only full match is considered. yes<br />
fms_score_match_rate_weight Specify the constant parameter k (weight on the match rate term) in FMS score 5<br />
fms_score_match_proj_cutoff Specify the scalar projection cutoff Ïƒ in the pharmacophore matching protocol. Default value cos(45 ï¿½ ) â‰ˆ 0.7071 corresponds to a vector angle cutoff of 45 ï¿½ 0.7071<br />
fms_score_max_score Specify the FMS score value for pharmacophore model pairs with no matches. This maximum FMS score depends on k, r and Ïƒ. 20</div>Lprentishttps://ringo.ams.stonybrook.edu/index.php?title=Scoring_Functions&diff=13101Scoring Functions2020-04-14T18:38:23Z<p>Lprentis: /* Pharmacophore Matching Similarity Score */</p>
<hr />
<div>DOCK uses several types of scoring functions to discriminate among orientations and molecules. Scoring is requested using the score_molecules parameter. A large portion of scoring functions can be called through descriptor score (but not all). Those with descriptor score functionality will be denoted in bold. <br />
<br />
== Continuous/DOCK Cartesian Energy Score==<br />
Continuous scoring may be used to evaluate a ligand:receptor complex without the investment of a grid calculation, or to perform a more detailed calculation without the numerical approximation of the grid. '''Continuous score is implemented under Descriptor Score as well'''. Continuous score is a cartesian based score and can be combined with other Cartesian based scores with very little computational expense.<br />
<br />
===Continuous/DCE Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
|continuous_score_primary<br />
| Does the user want to perform continuous non-grid scoring as the primary scoring function?<br />
| no<br />
|-<br />
|continuous_score_secondary <br />
| Does the user want to perform continuous non-grid scoring as the secondary scoring function? <br />
|no<br />
|-<br />
|cont_score_rec_filename <br />
|File that contains receptor coordinates <br />
|receptor.mol2<br />
|-<br />
|cont_score_att_exp <br />
|VDW Lennard-Jones potential attractive exponent <br />
|6<br />
|-<br />
|cont_score_rep_exp <br />
|VDW Lennard-Jones potential repulsive exponent <br />
|12<br />
|-<br />
|cont_score_rep_rad_scale <br />
|Scalar multiplier of the radii for the repulsive portion of the vdw energy component only <br />
|1.0<br />
|-<br />
|cont_score_use_dist_dep_dielectric <br />
|Distance dependent dielectric switch <br />
|yes<br />
|-<br />
|cont_score_dielectric <br />
|Dielectric constant for the electrostatic term <br />
|<br />
|- <br />
|cont_score_vdw_scale <br />
|Scalar multiplier of vdw energy component <br />
|1 <br />
|-<br />
|cont_score_vdw_scale <br />
|Flag to turn off vdw portion of the scoring function when cont_score_vdw_scale=0 <br />
|yes<br />
|- <br />
|cont_score_es_scale <br />
|Scalar multiplier of electrostatic energy component <br />
|1.0 <br />
|-<br />
|cont_score_turn_off_es <br />
|Flag to turn off es portion of the scoring function when cont_score_es_scale = 0 <br />
|yes<br />
|-<br />
|}<br />
<br />
===Continuous/DCE Score Output Components===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
|Continuous_score<br />
|sum of the van der Waals and electrostatic interactions<br />
|-<br />
|Continuous_vdw_energy<br />
|VDW interaction between ligand and receptor<br />
|-<br />
|Continuous_es_energy<br />
|ES interaction between the ligand and receptor<br />
|-<br />
|}<br />
<br />
==Grid-Based Score== <br />
DOCK needs a fast scoring function to evaluate poses rapidly during growth. The energy grid is used for this. The grid stores the non-bonded Molecular Mechanics Potential of the receptor at each grid point. <br />
[[Image:Mm-equation.png|center]]<br />
'''Grid can be called under descriptor score but it is suggested to not mix grid-based and cartesian space as that will dramatically increase computing time.'''<br />
===Grid Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
| grid_score_primary<br />
| Does the user want to perform grid-based energy scoring as the primary scoring function? || yes- <br />
|-<br />
| grid_score_rep_rad_scale<br />
| Scalar multiplier of the radii for the repulsive portion of the VDW energy component only when grid score is turned on || 1.0<br />
|-<br />
| grid_score_vdw_scale <br />
| Scalar multiplier of the VDW energy component || 1<br />
|-<br />
| grid_score_turn_off_vdw <br />
| A flag to turn off vdw portion of scoring function when grid score vdw scale = 0 || yes<br />
|-<br />
| grid_score_es_scale <br />
| Flag to scale up or down the es portion of the scoring function when es scale is turned on || 1<br />
|-<br />
| grid_score_turn_off_es <br />
| A flag to turn off es portion of scoring function when grid score es scale = 0 || yes<br />
|-<br />
| grid_score_grid_prefix <br />
| The prefix to the grid files containing the desired nrg/bmp grid || grid<br />
|-<br />
|}<br />
<br />
===Grid Score Output Components===<br />
These values will be printed in the header of the mol2 file post DOCK process.<br />
<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
| Grid_score<br />
| Sum of the VDW and ES interactions <br />
|-<br />
| Grid_vdw_energy<br />
| VDW interaction between the ligand grid<br />
|-<br />
| Grid_es_energy<br />
| ES interaction betweent eh ligand and grid<br />
|}<br />
<br />
==MultiGrid Score== <br />
The MultiGrid Score is similar to the Footprint Score described below, except that in the case of the Multi-Grid Score, the pair-wise interaction energies are computed over multiple grids rather than in Cartesian space. This is done to improve the tractability of FPS calculations as well as to make it simple to combine FPS and standard Grid Score. If the multiple grids are prepared as recommended than the sum of the interactions with each grid should equal the interaction of a standard DOCK grid representing the entire target. By default MultiGrid score will equal the sum of the interactions with all grids plus a FPS component generated by treating each grid as a protein residue. User defined scaling factors allow MultiGrid score to be set to equal Grid score, FPS score or any combination thereof. Generally, "important" receptor residues are identified before-hand based on the magnitude of their interaction with the reference ligand, then a unique grid is generated to represent each of those residues. Finally, a "remainder" grid is generated to represent all remaining receptor residues. The scoring function itself will then calculate intermolecular VDW and ES energies for the reference ligand and pose ligand on each of the grids (also called footprints), then it will calculate the footprint similarity using either the Standard Euclidean, Normalized Euclidean, or Pearson Correlation similarity metrics.<br />
<br />
'''MultiGrid can be called under descriptor score but it is suggested to not mix grid-based and cartesian space as that will dramatically increase computing time.'''<br />
<br />
===MultiGrid Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
| multigrid_score_primary<br />
| Does the user want to perform grid-based energy scoring as the primary scoring function? || yes- <br />
|-<br />
| multigrid_score_rep_rad_scale<br />
| Scalar multiplier of the radii for the repulsive portion of the VDW energy component only when grid score is turned on || 1.0<br />
|-<br />
| multigrid_score_vdw_scale <br />
| Scalar multiplier of the VDW energy component || 1<br />
|-<br />
| multigrid_score_es_scale <br />
| Flag to scale up or down the es portion of the scoring function when es scale is turned on || 1<br />
|-<br />
|multigrid_score_number_of_grids <br />
|Path to the reference txt file - only used when footprint reference txt is turned on. <br />
|ligand_footprint.txt<br />
|-<br />
|multigrid_score_grid_prefix0 <br />
|Provide prefixes to identify the grids. Note that the first grid starts at '0'. The last grid should be the remainder grid. This must be done for each grid. <br />
|multigrid0<br />
|-<br />
|multigrid_score_individual_rec_ensemble <br />
|Flag for individual receptor (standard) or multiple receptor (not implemented yet). <br />
|no<br />
|-<br />
|multigrid_score_weights_text <br />
|Flag for providing a textfile as input for the reference footprint. <br />
|no<br />
|-<br />
|multigrid_score_footprint_text <br />
|Name of the reference footprint input text file, when multigrid_score_weight_text is turned on. <br />
|reference.txt<br />
|-<br />
|multigrid_score_fp_ref_mol <br />
|Flag for providing a MOL2 as input for the reference footprint. <br />
|no<br />
|-<br />
|multigrid_score_footprint_ref <br />
|Name of the reference footprint input MOL2 file, when multigrid_score_fp_ref_mol is turned on. <br />
|reference.mol2<br />
|-<br />
|multigrid_score_foot_compare_type <br />
|Footprint similarity calculation methods (Options: Euclidean, Pearson). If Pearson, the correlation coefficient as the metric to compare the footprints. When the value is 1 then there is perfect agreement between the two footprints. WHen the value is 0 then there is poor agreement between the two footprints. If Euclidean, the Euclidean distance as the metric to compare the footprints. When the value is 0 then there is perfect agreement btween the two footprints. As the agreement gets worse between the two footprints the value increases. <br />
|Euclidean<br />
|-<br />
|multigrid_score_normalize_foot <br />
|normalization is used only with Euclidean distance. <br />
|no<br />
|-<br />
|multigrid_score_vdw_euc_scale <br />
|Scaling factor for VDW term. when using euclidean <br />
|1.0<br />
|-<br />
|multigrid_score_es_euc_scale <br />
|Scaling factor for ES term when using euclidean <br />
|1.0<br />
|-<br />
|multigrid_score_vdw_norm_scale <br />
|Scaling factor for VDW term. euclidean and normalize <br />
|10.0<br />
|-<br />
|multigrid_score_es_norm_scale <br />
|Scaling factor for ES term. Flags if using Pearson Correlation similarity metric for footprint comparison. <br />
|10.0<br />
|-<br />
|multigrid_score_vdw_cor_scale <br />
|Scaling factor for VDW term <br />
|(-10.0)<br />
|-<br />
|multigrid_score_es_cor_scale <br />
|Scaling factor for ES term <br />
|(-10.0)<br />
|-<br />
|}<br />
<br />
===MultiGrid Score Output Components===<br />
These values will be printed in the header of the mol2 file post DOCK process.<br />
<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
| MultiGrid_score<br />
| Sum of the VDW and ES interactions <br />
|-<br />
| MultiGrid_vdw_energy<br />
| VDW interaction between the ligand grid<br />
|-<br />
| MultiGrid_es_energy<br />
| ES interaction betweent eh ligand and grid<br />
|-<br />
| MGS_vdw+es_energy<br />
|sum of VDW and ES components<br />
|-<br />
|MGS_vdw_fps<br />
|VDW footprint similarity score<br />
|-<br />
|MGS_es_fps<br />
|ES footprint similarity score<br />
|-<br />
|MGS_vdw+es_fps<br />
|sum of VDW adn ES footprint similarity scores<br />
|-<br />
|}<br />
<br />
==Footprint Similarity Score==<br />
The Footprint Similarity Score is a scoring function that calculates intermolecular hydrogen bonds and footprint comparisons, in addition to standard intermolecular energies (VDW and ES). <br />
<br />
Intermolecular Energies (VDW, ES) are calculated the same way as in Continuous Score.<br />
<br />
A geometric definition of Hydrogen bonds is employed. We define 3 atoms XD, HD, and XA as the heavy atom donor, donated hydrogen, and heavy atom acceptor, respectively. There is a hydrogen bond present if the following two conditions are met:<br />
<br />
# The distance between HD and XA is less than or equal to 2.5 angstroms;<br />
# The angle defined by XD, HD, and XA is between 120 and 180 degrees.<br />
<br />
Footprints are a per-residue decomposition of interactions between the ligand and the receptor. This can be performed for all three terms VDW, ES, HB.<br />
Two footprints can be compared in three ways: Standard Euclidean, Normalized Euclidean, Pearson Correlation.<br />
<br />
Footprints are used to gauge how similar two poses or two molecules are to one-another. For applications to virtual screening applications a reference is required.<br />
<br />
There are to choices for a reference:<br />
<br />
# One can give a mol2 file containing a reference molecule, and footprints will be calculated.<br />
# One can pass a text file containing VDW, ES, and H-bond footprints. <br />
There are different choices for selection of residues:<br />
<br />
# All residues.<br />
# Residues chosen using a threshold (union of the sets of reference and pose). The VDW, ES, and HB footprints may have different residues chosen in this case.<br />
# Selected residues.<br />
<br />
Note that for (2) and (3) the remaining residue interaction may be placed in a remainder value included in the footprint.<br />
<br />
'''Footprint Similarity Score can be called under Descriptor Score.'''<br />
<br />
===Footprint Similarity Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
|footprint_similarity_score_primary <br />
|Flag to perform footprint scoring as the primary scoring function <br />
|no<br />
|-<br />
|footprint_similarity_score_secondary <br />
|Flag to perform footprint scoring as the secondary scoring function. <br />
|no<br />
|-<br />
|fps_score_use_footprint_reference_mol2 <br />
|Use a molecule to calculate footprint reference. <br />
|no<br />
|-<br />
|fps_score_footprint_reference_mol2_filename <br />
|Path to the reference mol2 file - only used when footprint reference mol2 is turned on. <br />
|ligand_footprint.mol2<br />
|-<br />
|fps_score_use_footprint_reference_txt <br />
|Use a pre-calculated footprint reference in text format. <br />
|no<br />
|-<br />
|fps_score_footprint_reference_txt_filename <br />
|Path to the reference txt file - only used when footprint reference txt is turned on. <br />
|ligand_footprint.txt<br />
|-<br />
|fps_score_foot_compare_type <br />
|Footprint similarity calculation methods (Options: Euclidean, Pearson). If Pearson, the correlation coefficient as the metric to compare the footprints. When the value is 1 then there is perfect agreement between the two footprints. WHen the value is 0 then there is poor agreement between the two footprints. If Euclidean, the Euclidean distance as the metric to compare the footprints. When the value is 0 then there is perfect agreement btween the two footprints. As the agreement gets worse between the two footprints the value increases. <br />
|Euclidean<br />
|-<br />
|fps_score_normalize_foot <br />
|normalization is used only with Euclidean distance. <br />
|no<br />
|-<br />
|fps_score_foot_comp_all_residue <br />
|If yes all residues are used for calculating the footprint. <br />
|yes<br />
|-<br />
|fps_score_choose_foot_range_type <br />
|User can use to determine the type of the range of the footprint by either specifying a residue range or defining a threshold. If specify_range, the user chooses to use a residue range and all footprints will be evaluated only on this residue range. First residue id = 1 not 0. If threshold, the user chose to use a residue range that is defined by only residues that have magnitudes that exceed the specified thresholds. (Options: specify_range, threshold) <br />
|specify_range<br />
|-<br />
|fps_score_vdw_threshold <br />
|Specify threshold for van der Waals energy, when threshold is turned on. <br />
|1<br />
|-<br />
|fps_score_es_threshold <br />
|Specify threshold for electrostatic energy, when threshold is turned on. <br />
|1<br />
|-<br />
|fps_score_hb_threshold <br />
|specify threshold for hydrogen bonds (integers). 0.5 means that all none zeros are used, when threshold is turned on. <br />
|0.5<br />
|-<br />
|fps_score_use_remainder <br />
|Interaction remainder is all remaining residues not included individually <br />
|yes<br />
|-<br />
|fps_score_rec_filename <br />
|File that contains receptor coordinates <br />
|receptor.mol2<br />
|-<br />
|fps_score_att_exp <br />
|VDW Lennard-Jones potential attractive exponent <br />
|6<br />
|-<br />
|fps_score_rep_exp <br />
|VDW Lennard-Jones potential repulsive exponent <br />
|12<br />
|-<br />
|fps_score_rep_rad_scale <br />
|Scalar multiplier of the radii for the repulsive portion of the VDW energy component ONLY <br />
|1<br />
|-<br />
|fps_score_use_distance_dependent_dielectric <br />
|Distance dependent dielectric switch <br />
|yes<br />
|-<br />
|fps_score_dielectric <br />
|Dielectric constant for electrostatic term <br />
|4.0<br />
|-<br />
|fps_score_vdw_scale <br />
|Scalar multiplier of vdw energy component <br />
|1<br />
|-<br />
|fps_score_es_scale <br />
|Scalar multiplier of es energy component <br />
|1<br />
|-<br />
|fps_score_hb_scale <br />
|Scalar multiplier of hb energy component <br />
|0<br />
|-<br />
|fps_score_internal_scale <br />
|Scalar multiplier of internal energy component <br />
|0<br />
|-<br />
|fps_score_fp_vwd_scale <br />
|Scalar multiplier of vdw footprint component <br />
|0<br />
|-<br />
|fps_score_fp_es_scale <br />
|Scalar multiplier of es footprint component <br />
|0<br />
|-<br />
|fps_score_fp_hb_scale <br />
|Scalar multiplier of hb footprint component <br />
|0<br />
|-<br />
|}<br />
<br />
===Footprint Similarity Score Output Components===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
|Footprint_similarity_score<br />
|sum of the van der Waals, electostatic, and hbond footprint similarity scores<br />
|-<br />
|FPS_vdw_energy<br />
|VDW interaction between ligand and receptor<br />
|-<br />
|FPS_es_energy<br />
|ES interaction between the ligand and receptor<br />
|-<br />
|FPS_num_hbond<br />
|number of hydrogen bonds<br />
|-<br />
|FPS_vdw+es_energy<br />
|sum of the van der Waals and electrostatic components<br />
|-<br />
|FPS_vdw_fps<br />
|vdw footprint similarity score<br />
|-<br />
|FPS_es_fps<br />
|ES footprint similarity score<br />
|-<br />
|FPS_hb_fps<br />
|hbond footprint similarity score<br />
|-<br />
|FPS_vdw_fp_numres<br />
|number of residues in the receptor considered during the calculation<br />
|-<br />
|FPS_es_fp_numres<br />
|number of residues in the receptor considered during the calculation<br />
|-<br />
|FPS_hb_fp_numres<br />
|number of residues in the receptor considered during the calculation<br />
|-<br />
|}<br />
<br />
==Pharmacophore Matching Similarity Score==<br />
The Pharmacophore Matching Similarity score is a scoring function that calculates the level of pharmacophore overlap between a reference molecule and a candidate molecule in three dimensional space.The functional form for quantifying the pharmacophore overlap in a virtual screening experiment using DOCK, termed pharmacophore matching similarity (FMS), is as follows:<br />
[[File:fms_equation.jpg]]<br />
<br />
'''Pharmacophore Matching Similarity Score can be called under Descriptor Score.''' <br />
<br />
===Pharmacophore Matching Similarity Score Parameters===</div>Lprentishttps://ringo.ams.stonybrook.edu/index.php?title=Scoring_Functions&diff=13100Scoring Functions2020-04-14T18:36:23Z<p>Lprentis: /* Grid-Based Score */</p>
<hr />
<div>DOCK uses several types of scoring functions to discriminate among orientations and molecules. Scoring is requested using the score_molecules parameter. A large portion of scoring functions can be called through descriptor score (but not all). Those with descriptor score functionality will be denoted in bold. <br />
<br />
== Continuous/DOCK Cartesian Energy Score==<br />
Continuous scoring may be used to evaluate a ligand:receptor complex without the investment of a grid calculation, or to perform a more detailed calculation without the numerical approximation of the grid. '''Continuous score is implemented under Descriptor Score as well'''. Continuous score is a cartesian based score and can be combined with other Cartesian based scores with very little computational expense.<br />
<br />
===Continuous/DCE Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
|continuous_score_primary<br />
| Does the user want to perform continuous non-grid scoring as the primary scoring function?<br />
| no<br />
|-<br />
|continuous_score_secondary <br />
| Does the user want to perform continuous non-grid scoring as the secondary scoring function? <br />
|no<br />
|-<br />
|cont_score_rec_filename <br />
|File that contains receptor coordinates <br />
|receptor.mol2<br />
|-<br />
|cont_score_att_exp <br />
|VDW Lennard-Jones potential attractive exponent <br />
|6<br />
|-<br />
|cont_score_rep_exp <br />
|VDW Lennard-Jones potential repulsive exponent <br />
|12<br />
|-<br />
|cont_score_rep_rad_scale <br />
|Scalar multiplier of the radii for the repulsive portion of the vdw energy component only <br />
|1.0<br />
|-<br />
|cont_score_use_dist_dep_dielectric <br />
|Distance dependent dielectric switch <br />
|yes<br />
|-<br />
|cont_score_dielectric <br />
|Dielectric constant for the electrostatic term <br />
|<br />
|- <br />
|cont_score_vdw_scale <br />
|Scalar multiplier of vdw energy component <br />
|1 <br />
|-<br />
|cont_score_vdw_scale <br />
|Flag to turn off vdw portion of the scoring function when cont_score_vdw_scale=0 <br />
|yes<br />
|- <br />
|cont_score_es_scale <br />
|Scalar multiplier of electrostatic energy component <br />
|1.0 <br />
|-<br />
|cont_score_turn_off_es <br />
|Flag to turn off es portion of the scoring function when cont_score_es_scale = 0 <br />
|yes<br />
|-<br />
|}<br />
<br />
===Continuous/DCE Score Output Components===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
|Continuous_score<br />
|sum of the van der Waals and electrostatic interactions<br />
|-<br />
|Continuous_vdw_energy<br />
|VDW interaction between ligand and receptor<br />
|-<br />
|Continuous_es_energy<br />
|ES interaction between the ligand and receptor<br />
|-<br />
|}<br />
<br />
==Grid-Based Score== <br />
DOCK needs a fast scoring function to evaluate poses rapidly during growth. The energy grid is used for this. The grid stores the non-bonded Molecular Mechanics Potential of the receptor at each grid point. <br />
[[Image:Mm-equation.png|center]]<br />
'''Grid can be called under descriptor score but it is suggested to not mix grid-based and cartesian space as that will dramatically increase computing time.'''<br />
===Grid Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
| grid_score_primary<br />
| Does the user want to perform grid-based energy scoring as the primary scoring function? || yes- <br />
|-<br />
| grid_score_rep_rad_scale<br />
| Scalar multiplier of the radii for the repulsive portion of the VDW energy component only when grid score is turned on || 1.0<br />
|-<br />
| grid_score_vdw_scale <br />
| Scalar multiplier of the VDW energy component || 1<br />
|-<br />
| grid_score_turn_off_vdw <br />
| A flag to turn off vdw portion of scoring function when grid score vdw scale = 0 || yes<br />
|-<br />
| grid_score_es_scale <br />
| Flag to scale up or down the es portion of the scoring function when es scale is turned on || 1<br />
|-<br />
| grid_score_turn_off_es <br />
| A flag to turn off es portion of scoring function when grid score es scale = 0 || yes<br />
|-<br />
| grid_score_grid_prefix <br />
| The prefix to the grid files containing the desired nrg/bmp grid || grid<br />
|-<br />
|}<br />
<br />
===Grid Score Output Components===<br />
These values will be printed in the header of the mol2 file post DOCK process.<br />
<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
| Grid_score<br />
| Sum of the VDW and ES interactions <br />
|-<br />
| Grid_vdw_energy<br />
| VDW interaction between the ligand grid<br />
|-<br />
| Grid_es_energy<br />
| ES interaction betweent eh ligand and grid<br />
|}<br />
<br />
==MultiGrid Score== <br />
The MultiGrid Score is similar to the Footprint Score described below, except that in the case of the Multi-Grid Score, the pair-wise interaction energies are computed over multiple grids rather than in Cartesian space. This is done to improve the tractability of FPS calculations as well as to make it simple to combine FPS and standard Grid Score. If the multiple grids are prepared as recommended than the sum of the interactions with each grid should equal the interaction of a standard DOCK grid representing the entire target. By default MultiGrid score will equal the sum of the interactions with all grids plus a FPS component generated by treating each grid as a protein residue. User defined scaling factors allow MultiGrid score to be set to equal Grid score, FPS score or any combination thereof. Generally, "important" receptor residues are identified before-hand based on the magnitude of their interaction with the reference ligand, then a unique grid is generated to represent each of those residues. Finally, a "remainder" grid is generated to represent all remaining receptor residues. The scoring function itself will then calculate intermolecular VDW and ES energies for the reference ligand and pose ligand on each of the grids (also called footprints), then it will calculate the footprint similarity using either the Standard Euclidean, Normalized Euclidean, or Pearson Correlation similarity metrics.<br />
<br />
'''MultiGrid can be called under descriptor score but it is suggested to not mix grid-based and cartesian space as that will dramatically increase computing time.'''<br />
<br />
===MultiGrid Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
| multigrid_score_primary<br />
| Does the user want to perform grid-based energy scoring as the primary scoring function? || yes- <br />
|-<br />
| multigrid_score_rep_rad_scale<br />
| Scalar multiplier of the radii for the repulsive portion of the VDW energy component only when grid score is turned on || 1.0<br />
|-<br />
| multigrid_score_vdw_scale <br />
| Scalar multiplier of the VDW energy component || 1<br />
|-<br />
| multigrid_score_es_scale <br />
| Flag to scale up or down the es portion of the scoring function when es scale is turned on || 1<br />
|-<br />
|multigrid_score_number_of_grids <br />
|Path to the reference txt file - only used when footprint reference txt is turned on. <br />
|ligand_footprint.txt<br />
|-<br />
|multigrid_score_grid_prefix0 <br />
|Provide prefixes to identify the grids. Note that the first grid starts at '0'. The last grid should be the remainder grid. This must be done for each grid. <br />
|multigrid0<br />
|-<br />
|multigrid_score_individual_rec_ensemble <br />
|Flag for individual receptor (standard) or multiple receptor (not implemented yet). <br />
|no<br />
|-<br />
|multigrid_score_weights_text <br />
|Flag for providing a textfile as input for the reference footprint. <br />
|no<br />
|-<br />
|multigrid_score_footprint_text <br />
|Name of the reference footprint input text file, when multigrid_score_weight_text is turned on. <br />
|reference.txt<br />
|-<br />
|multigrid_score_fp_ref_mol <br />
|Flag for providing a MOL2 as input for the reference footprint. <br />
|no<br />
|-<br />
|multigrid_score_footprint_ref <br />
|Name of the reference footprint input MOL2 file, when multigrid_score_fp_ref_mol is turned on. <br />
|reference.mol2<br />
|-<br />
|multigrid_score_foot_compare_type <br />
|Footprint similarity calculation methods (Options: Euclidean, Pearson). If Pearson, the correlation coefficient as the metric to compare the footprints. When the value is 1 then there is perfect agreement between the two footprints. WHen the value is 0 then there is poor agreement between the two footprints. If Euclidean, the Euclidean distance as the metric to compare the footprints. When the value is 0 then there is perfect agreement btween the two footprints. As the agreement gets worse between the two footprints the value increases. <br />
|Euclidean<br />
|-<br />
|multigrid_score_normalize_foot <br />
|normalization is used only with Euclidean distance. <br />
|no<br />
|-<br />
|multigrid_score_vdw_euc_scale <br />
|Scaling factor for VDW term. when using euclidean <br />
|1.0<br />
|-<br />
|multigrid_score_es_euc_scale <br />
|Scaling factor for ES term when using euclidean <br />
|1.0<br />
|-<br />
|multigrid_score_vdw_norm_scale <br />
|Scaling factor for VDW term. euclidean and normalize <br />
|10.0<br />
|-<br />
|multigrid_score_es_norm_scale <br />
|Scaling factor for ES term. Flags if using Pearson Correlation similarity metric for footprint comparison. <br />
|10.0<br />
|-<br />
|multigrid_score_vdw_cor_scale <br />
|Scaling factor for VDW term <br />
|(-10.0)<br />
|-<br />
|multigrid_score_es_cor_scale <br />
|Scaling factor for ES term <br />
|(-10.0)<br />
|-<br />
|}<br />
<br />
===MultiGrid Score Output Components===<br />
These values will be printed in the header of the mol2 file post DOCK process.<br />
<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
| MultiGrid_score<br />
| Sum of the VDW and ES interactions <br />
|-<br />
| MultiGrid_vdw_energy<br />
| VDW interaction between the ligand grid<br />
|-<br />
| MultiGrid_es_energy<br />
| ES interaction betweent eh ligand and grid<br />
|-<br />
| MGS_vdw+es_energy<br />
|sum of VDW and ES components<br />
|-<br />
|MGS_vdw_fps<br />
|VDW footprint similarity score<br />
|-<br />
|MGS_es_fps<br />
|ES footprint similarity score<br />
|-<br />
|MGS_vdw+es_fps<br />
|sum of VDW adn ES footprint similarity scores<br />
|-<br />
|}<br />
<br />
==Footprint Similarity Score==<br />
The Footprint Similarity Score is a scoring function that calculates intermolecular hydrogen bonds and footprint comparisons, in addition to standard intermolecular energies (VDW and ES). <br />
<br />
Intermolecular Energies (VDW, ES) are calculated the same way as in Continuous Score.<br />
<br />
A geometric definition of Hydrogen bonds is employed. We define 3 atoms XD, HD, and XA as the heavy atom donor, donated hydrogen, and heavy atom acceptor, respectively. There is a hydrogen bond present if the following two conditions are met:<br />
<br />
# The distance between HD and XA is less than or equal to 2.5 angstroms;<br />
# The angle defined by XD, HD, and XA is between 120 and 180 degrees.<br />
<br />
Footprints are a per-residue decomposition of interactions between the ligand and the receptor. This can be performed for all three terms VDW, ES, HB.<br />
Two footprints can be compared in three ways: Standard Euclidean, Normalized Euclidean, Pearson Correlation.<br />
<br />
Footprints are used to gauge how similar two poses or two molecules are to one-another. For applications to virtual screening applications a reference is required.<br />
<br />
There are to choices for a reference:<br />
<br />
# One can give a mol2 file containing a reference molecule, and footprints will be calculated.<br />
# One can pass a text file containing VDW, ES, and H-bond footprints. <br />
There are different choices for selection of residues:<br />
<br />
# All residues.<br />
# Residues chosen using a threshold (union of the sets of reference and pose). The VDW, ES, and HB footprints may have different residues chosen in this case.<br />
# Selected residues.<br />
<br />
Note that for (2) and (3) the remaining residue interaction may be placed in a remainder value included in the footprint.<br />
<br />
'''Footprint Similarity Score can be called under Descriptor Score.'''<br />
<br />
===Footprint Similarity Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
|footprint_similarity_score_primary <br />
|Flag to perform footprint scoring as the primary scoring function <br />
|no<br />
|-<br />
|footprint_similarity_score_secondary <br />
|Flag to perform footprint scoring as the secondary scoring function. <br />
|no<br />
|-<br />
|fps_score_use_footprint_reference_mol2 <br />
|Use a molecule to calculate footprint reference. <br />
|no<br />
|-<br />
|fps_score_footprint_reference_mol2_filename <br />
|Path to the reference mol2 file - only used when footprint reference mol2 is turned on. <br />
|ligand_footprint.mol2<br />
|-<br />
|fps_score_use_footprint_reference_txt <br />
|Use a pre-calculated footprint reference in text format. <br />
|no<br />
|-<br />
|fps_score_footprint_reference_txt_filename <br />
|Path to the reference txt file - only used when footprint reference txt is turned on. <br />
|ligand_footprint.txt<br />
|-<br />
|fps_score_foot_compare_type <br />
|Footprint similarity calculation methods (Options: Euclidean, Pearson). If Pearson, the correlation coefficient as the metric to compare the footprints. When the value is 1 then there is perfect agreement between the two footprints. WHen the value is 0 then there is poor agreement between the two footprints. If Euclidean, the Euclidean distance as the metric to compare the footprints. When the value is 0 then there is perfect agreement btween the two footprints. As the agreement gets worse between the two footprints the value increases. <br />
|Euclidean<br />
|-<br />
|fps_score_normalize_foot <br />
|normalization is used only with Euclidean distance. <br />
|no<br />
|-<br />
|fps_score_foot_comp_all_residue <br />
|If yes all residues are used for calculating the footprint. <br />
|yes<br />
|-<br />
|fps_score_choose_foot_range_type <br />
|User can use to determine the type of the range of the footprint by either specifying a residue range or defining a threshold. If specify_range, the user chooses to use a residue range and all footprints will be evaluated only on this residue range. First residue id = 1 not 0. If threshold, the user chose to use a residue range that is defined by only residues that have magnitudes that exceed the specified thresholds. (Options: specify_range, threshold) <br />
|specify_range<br />
|-<br />
|fps_score_vdw_threshold <br />
|Specify threshold for van der Waals energy, when threshold is turned on. <br />
|1<br />
|-<br />
|fps_score_es_threshold <br />
|Specify threshold for electrostatic energy, when threshold is turned on. <br />
|1<br />
|-<br />
|fps_score_hb_threshold <br />
|specify threshold for hydrogen bonds (integers). 0.5 means that all none zeros are used, when threshold is turned on. <br />
|0.5<br />
|-<br />
|fps_score_use_remainder <br />
|Interaction remainder is all remaining residues not included individually <br />
|yes<br />
|-<br />
|fps_score_rec_filename <br />
|File that contains receptor coordinates <br />
|receptor.mol2<br />
|-<br />
|fps_score_att_exp <br />
|VDW Lennard-Jones potential attractive exponent <br />
|6<br />
|-<br />
|fps_score_rep_exp <br />
|VDW Lennard-Jones potential repulsive exponent <br />
|12<br />
|-<br />
|fps_score_rep_rad_scale <br />
|Scalar multiplier of the radii for the repulsive portion of the VDW energy component ONLY <br />
|1<br />
|-<br />
|fps_score_use_distance_dependent_dielectric <br />
|Distance dependent dielectric switch <br />
|yes<br />
|-<br />
|fps_score_dielectric <br />
|Dielectric constant for electrostatic term <br />
|4.0<br />
|-<br />
|fps_score_vdw_scale <br />
|Scalar multiplier of vdw energy component <br />
|1<br />
|-<br />
|fps_score_es_scale <br />
|Scalar multiplier of es energy component <br />
|1<br />
|-<br />
|fps_score_hb_scale <br />
|Scalar multiplier of hb energy component <br />
|0<br />
|-<br />
|fps_score_internal_scale <br />
|Scalar multiplier of internal energy component <br />
|0<br />
|-<br />
|fps_score_fp_vwd_scale <br />
|Scalar multiplier of vdw footprint component <br />
|0<br />
|-<br />
|fps_score_fp_es_scale <br />
|Scalar multiplier of es footprint component <br />
|0<br />
|-<br />
|fps_score_fp_hb_scale <br />
|Scalar multiplier of hb footprint component <br />
|0<br />
|-<br />
|}<br />
<br />
===Footprint Similarity Score Output Components===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
|Footprint_similarity_score<br />
|sum of the van der Waals, electostatic, and hbond footprint similarity scores<br />
|-<br />
|FPS_vdw_energy<br />
|VDW interaction between ligand and receptor<br />
|-<br />
|FPS_es_energy<br />
|ES interaction between the ligand and receptor<br />
|-<br />
|FPS_num_hbond<br />
|number of hydrogen bonds<br />
|-<br />
|FPS_vdw+es_energy<br />
|sum of the van der Waals and electrostatic components<br />
|-<br />
|FPS_vdw_fps<br />
|vdw footprint similarity score<br />
|-<br />
|FPS_es_fps<br />
|ES footprint similarity score<br />
|-<br />
|FPS_hb_fps<br />
|hbond footprint similarity score<br />
|-<br />
|FPS_vdw_fp_numres<br />
|number of residues in the receptor considered during the calculation<br />
|-<br />
|FPS_es_fp_numres<br />
|number of residues in the receptor considered during the calculation<br />
|-<br />
|FPS_hb_fp_numres<br />
|number of residues in the receptor considered during the calculation<br />
|-<br />
|}<br />
<br />
==Pharmacophore Matching Similarity Score==<br />
The Pharmacophore Matching Similarity score is a scoring function that calculates the level of pharmacophore overlap between a reference molecule and a candidate molecule in three dimensional space.The functional form for quantifying the pharmacophore overlap in a virtual screening experiment using DOCK, termed pharmacophore matching similarity (FMS), is as follows:<br />
[[File:fms_equation.jpg]]</div>Lprentishttps://ringo.ams.stonybrook.edu/index.php?title=File:Fms_equation.jpg&diff=13099File:Fms equation.jpg2020-04-14T18:35:32Z<p>Lprentis: </p>
<hr />
<div></div>Lprentishttps://ringo.ams.stonybrook.edu/index.php?title=Scoring_Functions&diff=13098Scoring Functions2020-04-14T18:34:43Z<p>Lprentis: </p>
<hr />
<div>DOCK uses several types of scoring functions to discriminate among orientations and molecules. Scoring is requested using the score_molecules parameter. A large portion of scoring functions can be called through descriptor score (but not all). Those with descriptor score functionality will be denoted in bold. <br />
<br />
== Continuous/DOCK Cartesian Energy Score==<br />
Continuous scoring may be used to evaluate a ligand:receptor complex without the investment of a grid calculation, or to perform a more detailed calculation without the numerical approximation of the grid. '''Continuous score is implemented under Descriptor Score as well'''. Continuous score is a cartesian based score and can be combined with other Cartesian based scores with very little computational expense.<br />
<br />
===Continuous/DCE Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
|continuous_score_primary<br />
| Does the user want to perform continuous non-grid scoring as the primary scoring function?<br />
| no<br />
|-<br />
|continuous_score_secondary <br />
| Does the user want to perform continuous non-grid scoring as the secondary scoring function? <br />
|no<br />
|-<br />
|cont_score_rec_filename <br />
|File that contains receptor coordinates <br />
|receptor.mol2<br />
|-<br />
|cont_score_att_exp <br />
|VDW Lennard-Jones potential attractive exponent <br />
|6<br />
|-<br />
|cont_score_rep_exp <br />
|VDW Lennard-Jones potential repulsive exponent <br />
|12<br />
|-<br />
|cont_score_rep_rad_scale <br />
|Scalar multiplier of the radii for the repulsive portion of the vdw energy component only <br />
|1.0<br />
|-<br />
|cont_score_use_dist_dep_dielectric <br />
|Distance dependent dielectric switch <br />
|yes<br />
|-<br />
|cont_score_dielectric <br />
|Dielectric constant for the electrostatic term <br />
|<br />
|- <br />
|cont_score_vdw_scale <br />
|Scalar multiplier of vdw energy component <br />
|1 <br />
|-<br />
|cont_score_vdw_scale <br />
|Flag to turn off vdw portion of the scoring function when cont_score_vdw_scale=0 <br />
|yes<br />
|- <br />
|cont_score_es_scale <br />
|Scalar multiplier of electrostatic energy component <br />
|1.0 <br />
|-<br />
|cont_score_turn_off_es <br />
|Flag to turn off es portion of the scoring function when cont_score_es_scale = 0 <br />
|yes<br />
|-<br />
|}<br />
<br />
===Continuous/DCE Score Output Components===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
|Continuous_score<br />
|sum of the van der Waals and electrostatic interactions<br />
|-<br />
|Continuous_vdw_energy<br />
|VDW interaction between ligand and receptor<br />
|-<br />
|Continuous_es_energy<br />
|ES interaction between the ligand and receptor<br />
|-<br />
|}<br />
<br />
==Grid-Based Score== <br />
DOCK needs a fast scoring function to evaluate poses rapidly during growth. The energy grid is used for this. The grid stores the non-bonded Molecular Mechanics Potential of the receptor at each grid point. <br />
[[Image:Mm-equation.png|450px|center]]<br />
'''Grid can be called under descriptor score but it is suggested to not mix grid-based and cartesian space as that will dramatically increase computing time.'''<br />
===Grid Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
| grid_score_primary<br />
| Does the user want to perform grid-based energy scoring as the primary scoring function? || yes- <br />
|-<br />
| grid_score_rep_rad_scale<br />
| Scalar multiplier of the radii for the repulsive portion of the VDW energy component only when grid score is turned on || 1.0<br />
|-<br />
| grid_score_vdw_scale <br />
| Scalar multiplier of the VDW energy component || 1<br />
|-<br />
| grid_score_turn_off_vdw <br />
| A flag to turn off vdw portion of scoring function when grid score vdw scale = 0 || yes<br />
|-<br />
| grid_score_es_scale <br />
| Flag to scale up or down the es portion of the scoring function when es scale is turned on || 1<br />
|-<br />
| grid_score_turn_off_es <br />
| A flag to turn off es portion of scoring function when grid score es scale = 0 || yes<br />
|-<br />
| grid_score_grid_prefix <br />
| The prefix to the grid files containing the desired nrg/bmp grid || grid<br />
|-<br />
|}<br />
<br />
===Grid Score Output Components===<br />
These values will be printed in the header of the mol2 file post DOCK process.<br />
<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
| Grid_score<br />
| Sum of the VDW and ES interactions <br />
|-<br />
| Grid_vdw_energy<br />
| VDW interaction between the ligand grid<br />
|-<br />
| Grid_es_energy<br />
| ES interaction betweent eh ligand and grid<br />
|}<br />
<br />
==MultiGrid Score== <br />
The MultiGrid Score is similar to the Footprint Score described below, except that in the case of the Multi-Grid Score, the pair-wise interaction energies are computed over multiple grids rather than in Cartesian space. This is done to improve the tractability of FPS calculations as well as to make it simple to combine FPS and standard Grid Score. If the multiple grids are prepared as recommended than the sum of the interactions with each grid should equal the interaction of a standard DOCK grid representing the entire target. By default MultiGrid score will equal the sum of the interactions with all grids plus a FPS component generated by treating each grid as a protein residue. User defined scaling factors allow MultiGrid score to be set to equal Grid score, FPS score or any combination thereof. Generally, "important" receptor residues are identified before-hand based on the magnitude of their interaction with the reference ligand, then a unique grid is generated to represent each of those residues. Finally, a "remainder" grid is generated to represent all remaining receptor residues. The scoring function itself will then calculate intermolecular VDW and ES energies for the reference ligand and pose ligand on each of the grids (also called footprints), then it will calculate the footprint similarity using either the Standard Euclidean, Normalized Euclidean, or Pearson Correlation similarity metrics.<br />
<br />
'''MultiGrid can be called under descriptor score but it is suggested to not mix grid-based and cartesian space as that will dramatically increase computing time.'''<br />
<br />
===MultiGrid Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
| multigrid_score_primary<br />
| Does the user want to perform grid-based energy scoring as the primary scoring function? || yes- <br />
|-<br />
| multigrid_score_rep_rad_scale<br />
| Scalar multiplier of the radii for the repulsive portion of the VDW energy component only when grid score is turned on || 1.0<br />
|-<br />
| multigrid_score_vdw_scale <br />
| Scalar multiplier of the VDW energy component || 1<br />
|-<br />
| multigrid_score_es_scale <br />
| Flag to scale up or down the es portion of the scoring function when es scale is turned on || 1<br />
|-<br />
|multigrid_score_number_of_grids <br />
|Path to the reference txt file - only used when footprint reference txt is turned on. <br />
|ligand_footprint.txt<br />
|-<br />
|multigrid_score_grid_prefix0 <br />
|Provide prefixes to identify the grids. Note that the first grid starts at '0'. The last grid should be the remainder grid. This must be done for each grid. <br />
|multigrid0<br />
|-<br />
|multigrid_score_individual_rec_ensemble <br />
|Flag for individual receptor (standard) or multiple receptor (not implemented yet). <br />
|no<br />
|-<br />
|multigrid_score_weights_text <br />
|Flag for providing a textfile as input for the reference footprint. <br />
|no<br />
|-<br />
|multigrid_score_footprint_text <br />
|Name of the reference footprint input text file, when multigrid_score_weight_text is turned on. <br />
|reference.txt<br />
|-<br />
|multigrid_score_fp_ref_mol <br />
|Flag for providing a MOL2 as input for the reference footprint. <br />
|no<br />
|-<br />
|multigrid_score_footprint_ref <br />
|Name of the reference footprint input MOL2 file, when multigrid_score_fp_ref_mol is turned on. <br />
|reference.mol2<br />
|-<br />
|multigrid_score_foot_compare_type <br />
|Footprint similarity calculation methods (Options: Euclidean, Pearson). If Pearson, the correlation coefficient as the metric to compare the footprints. When the value is 1 then there is perfect agreement between the two footprints. WHen the value is 0 then there is poor agreement between the two footprints. If Euclidean, the Euclidean distance as the metric to compare the footprints. When the value is 0 then there is perfect agreement btween the two footprints. As the agreement gets worse between the two footprints the value increases. <br />
|Euclidean<br />
|-<br />
|multigrid_score_normalize_foot <br />
|normalization is used only with Euclidean distance. <br />
|no<br />
|-<br />
|multigrid_score_vdw_euc_scale <br />
|Scaling factor for VDW term. when using euclidean <br />
|1.0<br />
|-<br />
|multigrid_score_es_euc_scale <br />
|Scaling factor for ES term when using euclidean <br />
|1.0<br />
|-<br />
|multigrid_score_vdw_norm_scale <br />
|Scaling factor for VDW term. euclidean and normalize <br />
|10.0<br />
|-<br />
|multigrid_score_es_norm_scale <br />
|Scaling factor for ES term. Flags if using Pearson Correlation similarity metric for footprint comparison. <br />
|10.0<br />
|-<br />
|multigrid_score_vdw_cor_scale <br />
|Scaling factor for VDW term <br />
|(-10.0)<br />
|-<br />
|multigrid_score_es_cor_scale <br />
|Scaling factor for ES term <br />
|(-10.0)<br />
|-<br />
|}<br />
<br />
===MultiGrid Score Output Components===<br />
These values will be printed in the header of the mol2 file post DOCK process.<br />
<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
| MultiGrid_score<br />
| Sum of the VDW and ES interactions <br />
|-<br />
| MultiGrid_vdw_energy<br />
| VDW interaction between the ligand grid<br />
|-<br />
| MultiGrid_es_energy<br />
| ES interaction betweent eh ligand and grid<br />
|-<br />
| MGS_vdw+es_energy<br />
|sum of VDW and ES components<br />
|-<br />
|MGS_vdw_fps<br />
|VDW footprint similarity score<br />
|-<br />
|MGS_es_fps<br />
|ES footprint similarity score<br />
|-<br />
|MGS_vdw+es_fps<br />
|sum of VDW adn ES footprint similarity scores<br />
|-<br />
|}<br />
<br />
==Footprint Similarity Score==<br />
The Footprint Similarity Score is a scoring function that calculates intermolecular hydrogen bonds and footprint comparisons, in addition to standard intermolecular energies (VDW and ES). <br />
<br />
Intermolecular Energies (VDW, ES) are calculated the same way as in Continuous Score.<br />
<br />
A geometric definition of Hydrogen bonds is employed. We define 3 atoms XD, HD, and XA as the heavy atom donor, donated hydrogen, and heavy atom acceptor, respectively. There is a hydrogen bond present if the following two conditions are met:<br />
<br />
# The distance between HD and XA is less than or equal to 2.5 angstroms;<br />
# The angle defined by XD, HD, and XA is between 120 and 180 degrees.<br />
<br />
Footprints are a per-residue decomposition of interactions between the ligand and the receptor. This can be performed for all three terms VDW, ES, HB.<br />
Two footprints can be compared in three ways: Standard Euclidean, Normalized Euclidean, Pearson Correlation.<br />
<br />
Footprints are used to gauge how similar two poses or two molecules are to one-another. For applications to virtual screening applications a reference is required.<br />
<br />
There are to choices for a reference:<br />
<br />
# One can give a mol2 file containing a reference molecule, and footprints will be calculated.<br />
# One can pass a text file containing VDW, ES, and H-bond footprints. <br />
There are different choices for selection of residues:<br />
<br />
# All residues.<br />
# Residues chosen using a threshold (union of the sets of reference and pose). The VDW, ES, and HB footprints may have different residues chosen in this case.<br />
# Selected residues.<br />
<br />
Note that for (2) and (3) the remaining residue interaction may be placed in a remainder value included in the footprint.<br />
<br />
'''Footprint Similarity Score can be called under Descriptor Score.'''<br />
<br />
===Footprint Similarity Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
|footprint_similarity_score_primary <br />
|Flag to perform footprint scoring as the primary scoring function <br />
|no<br />
|-<br />
|footprint_similarity_score_secondary <br />
|Flag to perform footprint scoring as the secondary scoring function. <br />
|no<br />
|-<br />
|fps_score_use_footprint_reference_mol2 <br />
|Use a molecule to calculate footprint reference. <br />
|no<br />
|-<br />
|fps_score_footprint_reference_mol2_filename <br />
|Path to the reference mol2 file - only used when footprint reference mol2 is turned on. <br />
|ligand_footprint.mol2<br />
|-<br />
|fps_score_use_footprint_reference_txt <br />
|Use a pre-calculated footprint reference in text format. <br />
|no<br />
|-<br />
|fps_score_footprint_reference_txt_filename <br />
|Path to the reference txt file - only used when footprint reference txt is turned on. <br />
|ligand_footprint.txt<br />
|-<br />
|fps_score_foot_compare_type <br />
|Footprint similarity calculation methods (Options: Euclidean, Pearson). If Pearson, the correlation coefficient as the metric to compare the footprints. When the value is 1 then there is perfect agreement between the two footprints. WHen the value is 0 then there is poor agreement between the two footprints. If Euclidean, the Euclidean distance as the metric to compare the footprints. When the value is 0 then there is perfect agreement btween the two footprints. As the agreement gets worse between the two footprints the value increases. <br />
|Euclidean<br />
|-<br />
|fps_score_normalize_foot <br />
|normalization is used only with Euclidean distance. <br />
|no<br />
|-<br />
|fps_score_foot_comp_all_residue <br />
|If yes all residues are used for calculating the footprint. <br />
|yes<br />
|-<br />
|fps_score_choose_foot_range_type <br />
|User can use to determine the type of the range of the footprint by either specifying a residue range or defining a threshold. If specify_range, the user chooses to use a residue range and all footprints will be evaluated only on this residue range. First residue id = 1 not 0. If threshold, the user chose to use a residue range that is defined by only residues that have magnitudes that exceed the specified thresholds. (Options: specify_range, threshold) <br />
|specify_range<br />
|-<br />
|fps_score_vdw_threshold <br />
|Specify threshold for van der Waals energy, when threshold is turned on. <br />
|1<br />
|-<br />
|fps_score_es_threshold <br />
|Specify threshold for electrostatic energy, when threshold is turned on. <br />
|1<br />
|-<br />
|fps_score_hb_threshold <br />
|specify threshold for hydrogen bonds (integers). 0.5 means that all none zeros are used, when threshold is turned on. <br />
|0.5<br />
|-<br />
|fps_score_use_remainder <br />
|Interaction remainder is all remaining residues not included individually <br />
|yes<br />
|-<br />
|fps_score_rec_filename <br />
|File that contains receptor coordinates <br />
|receptor.mol2<br />
|-<br />
|fps_score_att_exp <br />
|VDW Lennard-Jones potential attractive exponent <br />
|6<br />
|-<br />
|fps_score_rep_exp <br />
|VDW Lennard-Jones potential repulsive exponent <br />
|12<br />
|-<br />
|fps_score_rep_rad_scale <br />
|Scalar multiplier of the radii for the repulsive portion of the VDW energy component ONLY <br />
|1<br />
|-<br />
|fps_score_use_distance_dependent_dielectric <br />
|Distance dependent dielectric switch <br />
|yes<br />
|-<br />
|fps_score_dielectric <br />
|Dielectric constant for electrostatic term <br />
|4.0<br />
|-<br />
|fps_score_vdw_scale <br />
|Scalar multiplier of vdw energy component <br />
|1<br />
|-<br />
|fps_score_es_scale <br />
|Scalar multiplier of es energy component <br />
|1<br />
|-<br />
|fps_score_hb_scale <br />
|Scalar multiplier of hb energy component <br />
|0<br />
|-<br />
|fps_score_internal_scale <br />
|Scalar multiplier of internal energy component <br />
|0<br />
|-<br />
|fps_score_fp_vwd_scale <br />
|Scalar multiplier of vdw footprint component <br />
|0<br />
|-<br />
|fps_score_fp_es_scale <br />
|Scalar multiplier of es footprint component <br />
|0<br />
|-<br />
|fps_score_fp_hb_scale <br />
|Scalar multiplier of hb footprint component <br />
|0<br />
|-<br />
|}<br />
<br />
===Footprint Similarity Score Output Components===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
|Footprint_similarity_score<br />
|sum of the van der Waals, electostatic, and hbond footprint similarity scores<br />
|-<br />
|FPS_vdw_energy<br />
|VDW interaction between ligand and receptor<br />
|-<br />
|FPS_es_energy<br />
|ES interaction between the ligand and receptor<br />
|-<br />
|FPS_num_hbond<br />
|number of hydrogen bonds<br />
|-<br />
|FPS_vdw+es_energy<br />
|sum of the van der Waals and electrostatic components<br />
|-<br />
|FPS_vdw_fps<br />
|vdw footprint similarity score<br />
|-<br />
|FPS_es_fps<br />
|ES footprint similarity score<br />
|-<br />
|FPS_hb_fps<br />
|hbond footprint similarity score<br />
|-<br />
|FPS_vdw_fp_numres<br />
|number of residues in the receptor considered during the calculation<br />
|-<br />
|FPS_es_fp_numres<br />
|number of residues in the receptor considered during the calculation<br />
|-<br />
|FPS_hb_fp_numres<br />
|number of residues in the receptor considered during the calculation<br />
|-<br />
|}<br />
<br />
==Pharmacophore Matching Similarity Score==<br />
The Pharmacophore Matching Similarity score is a scoring function that calculates the level of pharmacophore overlap between a reference molecule and a candidate molecule in three dimensional space.The functional form for quantifying the pharmacophore overlap in a virtual screening experiment using DOCK, termed pharmacophore matching similarity (FMS), is as follows:<br />
[[File:fms_equation.jpg]]</div>Lprentishttps://ringo.ams.stonybrook.edu/index.php?title=Scoring_Functions&diff=13097Scoring Functions2020-04-14T18:32:29Z<p>Lprentis: /* Continuous/DCE Score Output Components */</p>
<hr />
<div>DOCK uses several types of scoring functions to discriminate among orientations and molecules. Scoring is requested using the score_molecules parameter. A large portion of scoring functions can be called through descriptor score (but not all). Those with descriptor score functionality will be denoted in bold. <br />
<br />
== Continuous/DOCK Cartesian Energy Score==<br />
Continuous scoring may be used to evaluate a ligand:receptor complex without the investment of a grid calculation, or to perform a more detailed calculation without the numerical approximation of the grid. '''Continuous score is implemented under Descriptor Score as well'''. Continuous score is a cartesian based score and can be combined with other Cartesian based scores with very little computational expense.<br />
<br />
===Continuous/DCE Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
|continuous_score_primary<br />
| Does the user want to perform continuous non-grid scoring as the primary scoring function?<br />
| no<br />
|-<br />
|continuous_score_secondary <br />
| Does the user want to perform continuous non-grid scoring as the secondary scoring function? <br />
|no<br />
|-<br />
|cont_score_rec_filename <br />
|File that contains receptor coordinates <br />
|receptor.mol2<br />
|-<br />
|cont_score_att_exp <br />
|VDW Lennard-Jones potential attractive exponent <br />
|6<br />
|-<br />
|cont_score_rep_exp <br />
|VDW Lennard-Jones potential repulsive exponent <br />
|12<br />
|-<br />
|cont_score_rep_rad_scale <br />
|Scalar multiplier of the radii for the repulsive portion of the vdw energy component only <br />
|1.0<br />
|-<br />
|cont_score_use_dist_dep_dielectric <br />
|Distance dependent dielectric switch <br />
|yes<br />
|-<br />
|cont_score_dielectric <br />
|Dielectric constant for the electrostatic term <br />
|<br />
|- <br />
|cont_score_vdw_scale <br />
|Scalar multiplier of vdw energy component <br />
|1 <br />
|-<br />
|cont_score_vdw_scale <br />
|Flag to turn off vdw portion of the scoring function when cont_score_vdw_scale=0 <br />
|yes<br />
|- <br />
|cont_score_es_scale <br />
|Scalar multiplier of electrostatic energy component <br />
|1.0 <br />
|-<br />
|cont_score_turn_off_es <br />
|Flag to turn off es portion of the scoring function when cont_score_es_scale = 0 <br />
|yes<br />
|-<br />
|}<br />
<br />
===Continuous/DCE Score Output Components===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
|Continuous_score<br />
|sum of the van der Waals and electrostatic interactions<br />
|-<br />
|Continuous_vdw_energy<br />
|VDW interaction between ligand and receptor<br />
|-<br />
|Continuous_es_energy<br />
|ES interaction between the ligand and receptor<br />
|-<br />
|}<br />
<br />
==Grid-Based Score== <br />
DOCK needs a fast scoring function to evaluate poses rapidly during growth. The energy grid is used for this. The grid stores the non-bonded Molecular Mechanics Potential of the receptor at each grid point. <br />
[[Image:Mm-equation.png|450px|center]]<br />
'''Grid can be called under descriptor score but it is suggested to not mix grid-based and cartesian space as that will dramatically increase computing time.'''<br />
===Grid Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
| grid_score_primary<br />
| Does the user want to perform grid-based energy scoring as the primary scoring function? || yes- <br />
|-<br />
| grid_score_rep_rad_scale<br />
| Scalar multiplier of the radii for the repulsive portion of the VDW energy component only when grid score is turned on || 1.0<br />
|-<br />
| grid_score_vdw_scale <br />
| Scalar multiplier of the VDW energy component || 1<br />
|-<br />
| grid_score_turn_off_vdw <br />
| A flag to turn off vdw portion of scoring function when grid score vdw scale = 0 || yes<br />
|-<br />
| grid_score_es_scale <br />
| Flag to scale up or down the es portion of the scoring function when es scale is turned on || 1<br />
|-<br />
| grid_score_turn_off_es <br />
| A flag to turn off es portion of scoring function when grid score es scale = 0 || yes<br />
|-<br />
| grid_score_grid_prefix <br />
| The prefix to the grid files containing the desired nrg/bmp grid || grid<br />
|-<br />
|}<br />
<br />
===Grid Score Output Components===<br />
These values will be printed in the header of the mol2 file post DOCK process.<br />
<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
| Grid_score<br />
| Sum of the VDW and ES interactions <br />
|-<br />
| Grid_vdw_energy<br />
| VDW interaction between the ligand grid<br />
|-<br />
| Grid_es_energy<br />
| ES interaction betweent eh ligand and grid<br />
|}<br />
<br />
==MultiGrid Score== <br />
The MultiGrid Score is similar to the Footprint Score described below, except that in the case of the Multi-Grid Score, the pair-wise interaction energies are computed over multiple grids rather than in Cartesian space. This is done to improve the tractability of FPS calculations as well as to make it simple to combine FPS and standard Grid Score. If the multiple grids are prepared as recommended than the sum of the interactions with each grid should equal the interaction of a standard DOCK grid representing the entire target. By default MultiGrid score will equal the sum of the interactions with all grids plus a FPS component generated by treating each grid as a protein residue. User defined scaling factors allow MultiGrid score to be set to equal Grid score, FPS score or any combination thereof. Generally, "important" receptor residues are identified before-hand based on the magnitude of their interaction with the reference ligand, then a unique grid is generated to represent each of those residues. Finally, a "remainder" grid is generated to represent all remaining receptor residues. The scoring function itself will then calculate intermolecular VDW and ES energies for the reference ligand and pose ligand on each of the grids (also called footprints), then it will calculate the footprint similarity using either the Standard Euclidean, Normalized Euclidean, or Pearson Correlation similarity metrics.<br />
<br />
'''MultiGrid can be called under descriptor score but it is suggested to not mix grid-based and cartesian space as that will dramatically increase computing time.'''<br />
<br />
===MultiGrid Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
| multigrid_score_primary<br />
| Does the user want to perform grid-based energy scoring as the primary scoring function? || yes- <br />
|-<br />
| multigrid_score_rep_rad_scale<br />
| Scalar multiplier of the radii for the repulsive portion of the VDW energy component only when grid score is turned on || 1.0<br />
|-<br />
| multigrid_score_vdw_scale <br />
| Scalar multiplier of the VDW energy component || 1<br />
|-<br />
| multigrid_score_es_scale <br />
| Flag to scale up or down the es portion of the scoring function when es scale is turned on || 1<br />
|-<br />
|multigrid_score_number_of_grids <br />
|Path to the reference txt file - only used when footprint reference txt is turned on. <br />
|ligand_footprint.txt<br />
|-<br />
|multigrid_score_grid_prefix0 <br />
|Provide prefixes to identify the grids. Note that the first grid starts at '0'. The last grid should be the remainder grid. This must be done for each grid. <br />
|multigrid0<br />
|-<br />
|multigrid_score_individual_rec_ensemble <br />
|Flag for individual receptor (standard) or multiple receptor (not implemented yet). <br />
|no<br />
|-<br />
|multigrid_score_weights_text <br />
|Flag for providing a textfile as input for the reference footprint. <br />
|no<br />
|-<br />
|multigrid_score_footprint_text <br />
|Name of the reference footprint input text file, when multigrid_score_weight_text is turned on. <br />
|reference.txt<br />
|-<br />
|multigrid_score_fp_ref_mol <br />
|Flag for providing a MOL2 as input for the reference footprint. <br />
|no<br />
|-<br />
|multigrid_score_footprint_ref <br />
|Name of the reference footprint input MOL2 file, when multigrid_score_fp_ref_mol is turned on. <br />
|reference.mol2<br />
|-<br />
|multigrid_score_foot_compare_type <br />
|Footprint similarity calculation methods (Options: Euclidean, Pearson). If Pearson, the correlation coefficient as the metric to compare the footprints. When the value is 1 then there is perfect agreement between the two footprints. WHen the value is 0 then there is poor agreement between the two footprints. If Euclidean, the Euclidean distance as the metric to compare the footprints. When the value is 0 then there is perfect agreement btween the two footprints. As the agreement gets worse between the two footprints the value increases. <br />
|Euclidean<br />
|-<br />
|multigrid_score_normalize_foot <br />
|normalization is used only with Euclidean distance. <br />
|no<br />
|-<br />
|multigrid_score_vdw_euc_scale <br />
|Scaling factor for VDW term. when using euclidean <br />
|1.0<br />
|-<br />
|multigrid_score_es_euc_scale <br />
|Scaling factor for ES term when using euclidean <br />
|1.0<br />
|-<br />
|multigrid_score_vdw_norm_scale <br />
|Scaling factor for VDW term. euclidean and normalize <br />
|10.0<br />
|-<br />
|multigrid_score_es_norm_scale <br />
|Scaling factor for ES term. Flags if using Pearson Correlation similarity metric for footprint comparison. <br />
|10.0<br />
|-<br />
|multigrid_score_vdw_cor_scale <br />
|Scaling factor for VDW term <br />
|(-10.0)<br />
|-<br />
|multigrid_score_es_cor_scale <br />
|Scaling factor for ES term <br />
|(-10.0)<br />
|-<br />
|}<br />
<br />
===MultiGrid Score Output Components===<br />
These values will be printed in the header of the mol2 file post DOCK process.<br />
<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
| MultiGrid_score<br />
| Sum of the VDW and ES interactions <br />
|-<br />
| MultiGrid_vdw_energy<br />
| VDW interaction between the ligand grid<br />
|-<br />
| MultiGrid_es_energy<br />
| ES interaction betweent eh ligand and grid<br />
|-<br />
| MGS_vdw+es_energy<br />
|sum of VDW and ES components<br />
|-<br />
|MGS_vdw_fps<br />
|VDW footprint similarity score<br />
|-<br />
|MGS_es_fps<br />
|ES footprint similarity score<br />
|-<br />
|MGS_vdw+es_fps<br />
|sum of VDW adn ES footprint similarity scores<br />
|-<br />
|}<br />
<br />
==Footprint Similarity Score==<br />
The Footprint Similarity Score is a scoring function that calculates intermolecular hydrogen bonds and footprint comparisons, in addition to standard intermolecular energies (VDW and ES). <br />
<br />
Intermolecular Energies (VDW, ES) are calculated the same way as in Continuous Score.<br />
<br />
A geometric definition of Hydrogen bonds is employed. We define 3 atoms XD, HD, and XA as the heavy atom donor, donated hydrogen, and heavy atom acceptor, respectively. There is a hydrogen bond present if the following two conditions are met:<br />
<br />
# The distance between HD and XA is less than or equal to 2.5 angstroms;<br />
# The angle defined by XD, HD, and XA is between 120 and 180 degrees.<br />
<br />
Footprints are a per-residue decomposition of interactions between the ligand and the receptor. This can be performed for all three terms VDW, ES, HB.<br />
Two footprints can be compared in three ways: Standard Euclidean, Normalized Euclidean, Pearson Correlation.<br />
<br />
Footprints are used to gauge how similar two poses or two molecules are to one-another. For applications to virtual screening applications a reference is required.<br />
<br />
There are to choices for a reference:<br />
<br />
# One can give a mol2 file containing a reference molecule, and footprints will be calculated.<br />
# One can pass a text file containing VDW, ES, and H-bond footprints. <br />
There are different choices for selection of residues:<br />
<br />
# All residues.<br />
# Residues chosen using a threshold (union of the sets of reference and pose). The VDW, ES, and HB footprints may have different residues chosen in this case.<br />
# Selected residues.<br />
<br />
Note that for (2) and (3) the remaining residue interaction may be placed in a remainder value included in the footprint.<br />
<br />
'''Footprint Similarity Score can be called under Descriptor Score.'''<br />
<br />
===Footprint Similarity Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
|footprint_similarity_score_primary <br />
|Flag to perform footprint scoring as the primary scoring function <br />
|no<br />
|-<br />
|footprint_similarity_score_secondary <br />
|Flag to perform footprint scoring as the secondary scoring function. <br />
|no<br />
|-<br />
|fps_score_use_footprint_reference_mol2 <br />
|Use a molecule to calculate footprint reference. <br />
|no<br />
|-<br />
|fps_score_footprint_reference_mol2_filename <br />
|Path to the reference mol2 file - only used when footprint reference mol2 is turned on. <br />
|ligand_footprint.mol2<br />
|-<br />
|fps_score_use_footprint_reference_txt <br />
|Use a pre-calculated footprint reference in text format. <br />
|no<br />
|-<br />
|fps_score_footprint_reference_txt_filename <br />
|Path to the reference txt file - only used when footprint reference txt is turned on. <br />
|ligand_footprint.txt<br />
|-<br />
|fps_score_foot_compare_type <br />
|Footprint similarity calculation methods (Options: Euclidean, Pearson). If Pearson, the correlation coefficient as the metric to compare the footprints. When the value is 1 then there is perfect agreement between the two footprints. WHen the value is 0 then there is poor agreement between the two footprints. If Euclidean, the Euclidean distance as the metric to compare the footprints. When the value is 0 then there is perfect agreement btween the two footprints. As the agreement gets worse between the two footprints the value increases. <br />
|Euclidean<br />
|-<br />
|fps_score_normalize_foot <br />
|normalization is used only with Euclidean distance. <br />
|no<br />
|-<br />
|fps_score_foot_comp_all_residue <br />
|If yes all residues are used for calculating the footprint. <br />
|yes<br />
|-<br />
|fps_score_choose_foot_range_type <br />
|User can use to determine the type of the range of the footprint by either specifying a residue range or defining a threshold. If specify_range, the user chooses to use a residue range and all footprints will be evaluated only on this residue range. First residue id = 1 not 0. If threshold, the user chose to use a residue range that is defined by only residues that have magnitudes that exceed the specified thresholds. (Options: specify_range, threshold) <br />
|specify_range<br />
|-<br />
|fps_score_vdw_threshold <br />
|Specify threshold for van der Waals energy, when threshold is turned on. <br />
|1<br />
|-<br />
|fps_score_es_threshold <br />
|Specify threshold for electrostatic energy, when threshold is turned on. <br />
|1<br />
|-<br />
|fps_score_hb_threshold <br />
|specify threshold for hydrogen bonds (integers). 0.5 means that all none zeros are used, when threshold is turned on. <br />
|0.5<br />
|-<br />
|fps_score_use_remainder <br />
|Interaction remainder is all remaining residues not included individually <br />
|yes<br />
|-<br />
|fps_score_rec_filename <br />
|File that contains receptor coordinates <br />
|receptor.mol2<br />
|-<br />
|fps_score_att_exp <br />
|VDW Lennard-Jones potential attractive exponent <br />
|6<br />
|-<br />
|fps_score_rep_exp <br />
|VDW Lennard-Jones potential repulsive exponent <br />
|12<br />
|-<br />
|fps_score_rep_rad_scale <br />
|Scalar multiplier of the radii for the repulsive portion of the VDW energy component ONLY <br />
|1<br />
|-<br />
|fps_score_use_distance_dependent_dielectric <br />
|Distance dependent dielectric switch <br />
|yes<br />
|-<br />
|fps_score_dielectric <br />
|Dielectric constant for electrostatic term <br />
|4.0<br />
|-<br />
|fps_score_vdw_scale <br />
|Scalar multiplier of vdw energy component <br />
|1<br />
|-<br />
|fps_score_es_scale <br />
|Scalar multiplier of es energy component <br />
|1<br />
|-<br />
|fps_score_hb_scale <br />
|Scalar multiplier of hb energy component <br />
|0<br />
|-<br />
|fps_score_internal_scale <br />
|Scalar multiplier of internal energy component <br />
|0<br />
|-<br />
|fps_score_fp_vwd_scale <br />
|Scalar multiplier of vdw footprint component <br />
|0<br />
|-<br />
|fps_score_fp_es_scale <br />
|Scalar multiplier of es footprint component <br />
|0<br />
|-<br />
|fps_score_fp_hb_scale <br />
|Scalar multiplier of hb footprint component <br />
|0<br />
|-<br />
|}<br />
<br />
===Footprint Similarity Score Output Components===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
|Footprint_similarity_score<br />
|sum of the van der Waals, electostatic, and hbond footprint similarity scores<br />
|-<br />
|FPS_vdw_energy<br />
|VDW interaction between ligand and receptor<br />
|-<br />
|FPS_es_energy<br />
|ES interaction between the ligand and receptor<br />
|-<br />
|FPS_num_hbond<br />
|number of hydrogen bonds<br />
|-<br />
|FPS_vdw+es_energy<br />
|sum of the van der Waals and electrostatic components<br />
|-<br />
|FPS_vdw_fps<br />
|vdw footprint similarity score<br />
|-<br />
|FPS_es_fps<br />
|ES footprint similarity score<br />
|-<br />
|FPS_hb_fps<br />
|hbond footprint similarity score<br />
|-<br />
|FPS_vdw_fp_numres<br />
|number of residues in the receptor considered during the calculation<br />
|-<br />
|FPS_es_fp_numres<br />
|number of residues in the receptor considered during the calculation<br />
|-<br />
|FPS_hb_fp_numres<br />
|number of residues in the receptor considered during the calculation<br />
|-<br />
|}</div>Lprentishttps://ringo.ams.stonybrook.edu/index.php?title=Scoring_Functions&diff=13096Scoring Functions2020-04-14T18:28:36Z<p>Lprentis: /* MultiGrid Score Output Components */</p>
<hr />
<div>DOCK uses several types of scoring functions to discriminate among orientations and molecules. Scoring is requested using the score_molecules parameter. A large portion of scoring functions can be called through descriptor score (but not all). Those with descriptor score functionality will be denoted in bold. <br />
<br />
== Continuous/DOCK Cartesian Energy Score==<br />
Continuous scoring may be used to evaluate a ligand:receptor complex without the investment of a grid calculation, or to perform a more detailed calculation without the numerical approximation of the grid. '''Continuous score is implemented under Descriptor Score as well'''. Continuous score is a cartesian based score and can be combined with other Cartesian based scores with very little computational expense.<br />
<br />
===Continuous/DCE Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
|continuous_score_primary<br />
| Does the user want to perform continuous non-grid scoring as the primary scoring function?<br />
| no<br />
|-<br />
|continuous_score_secondary <br />
| Does the user want to perform continuous non-grid scoring as the secondary scoring function? <br />
|no<br />
|-<br />
|cont_score_rec_filename <br />
|File that contains receptor coordinates <br />
|receptor.mol2<br />
|-<br />
|cont_score_att_exp <br />
|VDW Lennard-Jones potential attractive exponent <br />
|6<br />
|-<br />
|cont_score_rep_exp <br />
|VDW Lennard-Jones potential repulsive exponent <br />
|12<br />
|-<br />
|cont_score_rep_rad_scale <br />
|Scalar multiplier of the radii for the repulsive portion of the vdw energy component only <br />
|1.0<br />
|-<br />
|cont_score_use_dist_dep_dielectric <br />
|Distance dependent dielectric switch <br />
|yes<br />
|-<br />
|cont_score_dielectric <br />
|Dielectric constant for the electrostatic term <br />
|<br />
|- <br />
|cont_score_vdw_scale <br />
|Scalar multiplier of vdw energy component <br />
|1 <br />
|-<br />
|cont_score_vdw_scale <br />
|Flag to turn off vdw portion of the scoring function when cont_score_vdw_scale=0 <br />
|yes<br />
|- <br />
|cont_score_es_scale <br />
|Scalar multiplier of electrostatic energy component <br />
|1.0 <br />
|-<br />
|cont_score_turn_off_es <br />
|Flag to turn off es portion of the scoring function when cont_score_es_scale = 0 <br />
|yes<br />
|-<br />
|}<br />
<br />
===Continuous/DCE Score Output Components===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
|Continuous-score<br />
|sum of the van der Waals and electrostatic interactions<br />
|-<br />
|Continuous_vdw_energy<br />
|VDW interaction between ligand and receptor<br />
|-<br />
|Continuous_es_energy<br />
|ES interaction between the ligand and receptor<br />
|-<br />
|}<br />
<br />
==Grid-Based Score== <br />
DOCK needs a fast scoring function to evaluate poses rapidly during growth. The energy grid is used for this. The grid stores the non-bonded Molecular Mechanics Potential of the receptor at each grid point. <br />
[[Image:Mm-equation.png|450px|center]]<br />
'''Grid can be called under descriptor score but it is suggested to not mix grid-based and cartesian space as that will dramatically increase computing time.'''<br />
===Grid Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
| grid_score_primary<br />
| Does the user want to perform grid-based energy scoring as the primary scoring function? || yes- <br />
|-<br />
| grid_score_rep_rad_scale<br />
| Scalar multiplier of the radii for the repulsive portion of the VDW energy component only when grid score is turned on || 1.0<br />
|-<br />
| grid_score_vdw_scale <br />
| Scalar multiplier of the VDW energy component || 1<br />
|-<br />
| grid_score_turn_off_vdw <br />
| A flag to turn off vdw portion of scoring function when grid score vdw scale = 0 || yes<br />
|-<br />
| grid_score_es_scale <br />
| Flag to scale up or down the es portion of the scoring function when es scale is turned on || 1<br />
|-<br />
| grid_score_turn_off_es <br />
| A flag to turn off es portion of scoring function when grid score es scale = 0 || yes<br />
|-<br />
| grid_score_grid_prefix <br />
| The prefix to the grid files containing the desired nrg/bmp grid || grid<br />
|-<br />
|}<br />
<br />
===Grid Score Output Components===<br />
These values will be printed in the header of the mol2 file post DOCK process.<br />
<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
| Grid_score<br />
| Sum of the VDW and ES interactions <br />
|-<br />
| Grid_vdw_energy<br />
| VDW interaction between the ligand grid<br />
|-<br />
| Grid_es_energy<br />
| ES interaction betweent eh ligand and grid<br />
|}<br />
<br />
==MultiGrid Score== <br />
The MultiGrid Score is similar to the Footprint Score described below, except that in the case of the Multi-Grid Score, the pair-wise interaction energies are computed over multiple grids rather than in Cartesian space. This is done to improve the tractability of FPS calculations as well as to make it simple to combine FPS and standard Grid Score. If the multiple grids are prepared as recommended than the sum of the interactions with each grid should equal the interaction of a standard DOCK grid representing the entire target. By default MultiGrid score will equal the sum of the interactions with all grids plus a FPS component generated by treating each grid as a protein residue. User defined scaling factors allow MultiGrid score to be set to equal Grid score, FPS score or any combination thereof. Generally, "important" receptor residues are identified before-hand based on the magnitude of their interaction with the reference ligand, then a unique grid is generated to represent each of those residues. Finally, a "remainder" grid is generated to represent all remaining receptor residues. The scoring function itself will then calculate intermolecular VDW and ES energies for the reference ligand and pose ligand on each of the grids (also called footprints), then it will calculate the footprint similarity using either the Standard Euclidean, Normalized Euclidean, or Pearson Correlation similarity metrics.<br />
<br />
'''MultiGrid can be called under descriptor score but it is suggested to not mix grid-based and cartesian space as that will dramatically increase computing time.'''<br />
<br />
===MultiGrid Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
| multigrid_score_primary<br />
| Does the user want to perform grid-based energy scoring as the primary scoring function? || yes- <br />
|-<br />
| multigrid_score_rep_rad_scale<br />
| Scalar multiplier of the radii for the repulsive portion of the VDW energy component only when grid score is turned on || 1.0<br />
|-<br />
| multigrid_score_vdw_scale <br />
| Scalar multiplier of the VDW energy component || 1<br />
|-<br />
| multigrid_score_es_scale <br />
| Flag to scale up or down the es portion of the scoring function when es scale is turned on || 1<br />
|-<br />
|multigrid_score_number_of_grids <br />
|Path to the reference txt file - only used when footprint reference txt is turned on. <br />
|ligand_footprint.txt<br />
|-<br />
|multigrid_score_grid_prefix0 <br />
|Provide prefixes to identify the grids. Note that the first grid starts at '0'. The last grid should be the remainder grid. This must be done for each grid. <br />
|multigrid0<br />
|-<br />
|multigrid_score_individual_rec_ensemble <br />
|Flag for individual receptor (standard) or multiple receptor (not implemented yet). <br />
|no<br />
|-<br />
|multigrid_score_weights_text <br />
|Flag for providing a textfile as input for the reference footprint. <br />
|no<br />
|-<br />
|multigrid_score_footprint_text <br />
|Name of the reference footprint input text file, when multigrid_score_weight_text is turned on. <br />
|reference.txt<br />
|-<br />
|multigrid_score_fp_ref_mol <br />
|Flag for providing a MOL2 as input for the reference footprint. <br />
|no<br />
|-<br />
|multigrid_score_footprint_ref <br />
|Name of the reference footprint input MOL2 file, when multigrid_score_fp_ref_mol is turned on. <br />
|reference.mol2<br />
|-<br />
|multigrid_score_foot_compare_type <br />
|Footprint similarity calculation methods (Options: Euclidean, Pearson). If Pearson, the correlation coefficient as the metric to compare the footprints. When the value is 1 then there is perfect agreement between the two footprints. WHen the value is 0 then there is poor agreement between the two footprints. If Euclidean, the Euclidean distance as the metric to compare the footprints. When the value is 0 then there is perfect agreement btween the two footprints. As the agreement gets worse between the two footprints the value increases. <br />
|Euclidean<br />
|-<br />
|multigrid_score_normalize_foot <br />
|normalization is used only with Euclidean distance. <br />
|no<br />
|-<br />
|multigrid_score_vdw_euc_scale <br />
|Scaling factor for VDW term. when using euclidean <br />
|1.0<br />
|-<br />
|multigrid_score_es_euc_scale <br />
|Scaling factor for ES term when using euclidean <br />
|1.0<br />
|-<br />
|multigrid_score_vdw_norm_scale <br />
|Scaling factor for VDW term. euclidean and normalize <br />
|10.0<br />
|-<br />
|multigrid_score_es_norm_scale <br />
|Scaling factor for ES term. Flags if using Pearson Correlation similarity metric for footprint comparison. <br />
|10.0<br />
|-<br />
|multigrid_score_vdw_cor_scale <br />
|Scaling factor for VDW term <br />
|(-10.0)<br />
|-<br />
|multigrid_score_es_cor_scale <br />
|Scaling factor for ES term <br />
|(-10.0)<br />
|-<br />
|}<br />
<br />
===MultiGrid Score Output Components===<br />
These values will be printed in the header of the mol2 file post DOCK process.<br />
<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
| MultiGrid_score<br />
| Sum of the VDW and ES interactions <br />
|-<br />
| MultiGrid_vdw_energy<br />
| VDW interaction between the ligand grid<br />
|-<br />
| MultiGrid_es_energy<br />
| ES interaction betweent eh ligand and grid<br />
|-<br />
| MGS_vdw+es_energy<br />
|sum of VDW and ES components<br />
|-<br />
|MGS_vdw_fps<br />
|VDW footprint similarity score<br />
|-<br />
|MGS_es_fps<br />
|ES footprint similarity score<br />
|-<br />
|MGS_vdw+es_fps<br />
|sum of VDW adn ES footprint similarity scores<br />
|-<br />
|}<br />
<br />
==Footprint Similarity Score==<br />
The Footprint Similarity Score is a scoring function that calculates intermolecular hydrogen bonds and footprint comparisons, in addition to standard intermolecular energies (VDW and ES). <br />
<br />
Intermolecular Energies (VDW, ES) are calculated the same way as in Continuous Score.<br />
<br />
A geometric definition of Hydrogen bonds is employed. We define 3 atoms XD, HD, and XA as the heavy atom donor, donated hydrogen, and heavy atom acceptor, respectively. There is a hydrogen bond present if the following two conditions are met:<br />
<br />
# The distance between HD and XA is less than or equal to 2.5 angstroms;<br />
# The angle defined by XD, HD, and XA is between 120 and 180 degrees.<br />
<br />
Footprints are a per-residue decomposition of interactions between the ligand and the receptor. This can be performed for all three terms VDW, ES, HB.<br />
Two footprints can be compared in three ways: Standard Euclidean, Normalized Euclidean, Pearson Correlation.<br />
<br />
Footprints are used to gauge how similar two poses or two molecules are to one-another. For applications to virtual screening applications a reference is required.<br />
<br />
There are to choices for a reference:<br />
<br />
# One can give a mol2 file containing a reference molecule, and footprints will be calculated.<br />
# One can pass a text file containing VDW, ES, and H-bond footprints. <br />
There are different choices for selection of residues:<br />
<br />
# All residues.<br />
# Residues chosen using a threshold (union of the sets of reference and pose). The VDW, ES, and HB footprints may have different residues chosen in this case.<br />
# Selected residues.<br />
<br />
Note that for (2) and (3) the remaining residue interaction may be placed in a remainder value included in the footprint.<br />
<br />
'''Footprint Similarity Score can be called under Descriptor Score.'''<br />
<br />
===Footprint Similarity Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
|footprint_similarity_score_primary <br />
|Flag to perform footprint scoring as the primary scoring function <br />
|no<br />
|-<br />
|footprint_similarity_score_secondary <br />
|Flag to perform footprint scoring as the secondary scoring function. <br />
|no<br />
|-<br />
|fps_score_use_footprint_reference_mol2 <br />
|Use a molecule to calculate footprint reference. <br />
|no<br />
|-<br />
|fps_score_footprint_reference_mol2_filename <br />
|Path to the reference mol2 file - only used when footprint reference mol2 is turned on. <br />
|ligand_footprint.mol2<br />
|-<br />
|fps_score_use_footprint_reference_txt <br />
|Use a pre-calculated footprint reference in text format. <br />
|no<br />
|-<br />
|fps_score_footprint_reference_txt_filename <br />
|Path to the reference txt file - only used when footprint reference txt is turned on. <br />
|ligand_footprint.txt<br />
|-<br />
|fps_score_foot_compare_type <br />
|Footprint similarity calculation methods (Options: Euclidean, Pearson). If Pearson, the correlation coefficient as the metric to compare the footprints. When the value is 1 then there is perfect agreement between the two footprints. WHen the value is 0 then there is poor agreement between the two footprints. If Euclidean, the Euclidean distance as the metric to compare the footprints. When the value is 0 then there is perfect agreement btween the two footprints. As the agreement gets worse between the two footprints the value increases. <br />
|Euclidean<br />
|-<br />
|fps_score_normalize_foot <br />
|normalization is used only with Euclidean distance. <br />
|no<br />
|-<br />
|fps_score_foot_comp_all_residue <br />
|If yes all residues are used for calculating the footprint. <br />
|yes<br />
|-<br />
|fps_score_choose_foot_range_type <br />
|User can use to determine the type of the range of the footprint by either specifying a residue range or defining a threshold. If specify_range, the user chooses to use a residue range and all footprints will be evaluated only on this residue range. First residue id = 1 not 0. If threshold, the user chose to use a residue range that is defined by only residues that have magnitudes that exceed the specified thresholds. (Options: specify_range, threshold) <br />
|specify_range<br />
|-<br />
|fps_score_vdw_threshold <br />
|Specify threshold for van der Waals energy, when threshold is turned on. <br />
|1<br />
|-<br />
|fps_score_es_threshold <br />
|Specify threshold for electrostatic energy, when threshold is turned on. <br />
|1<br />
|-<br />
|fps_score_hb_threshold <br />
|specify threshold for hydrogen bonds (integers). 0.5 means that all none zeros are used, when threshold is turned on. <br />
|0.5<br />
|-<br />
|fps_score_use_remainder <br />
|Interaction remainder is all remaining residues not included individually <br />
|yes<br />
|-<br />
|fps_score_rec_filename <br />
|File that contains receptor coordinates <br />
|receptor.mol2<br />
|-<br />
|fps_score_att_exp <br />
|VDW Lennard-Jones potential attractive exponent <br />
|6<br />
|-<br />
|fps_score_rep_exp <br />
|VDW Lennard-Jones potential repulsive exponent <br />
|12<br />
|-<br />
|fps_score_rep_rad_scale <br />
|Scalar multiplier of the radii for the repulsive portion of the VDW energy component ONLY <br />
|1<br />
|-<br />
|fps_score_use_distance_dependent_dielectric <br />
|Distance dependent dielectric switch <br />
|yes<br />
|-<br />
|fps_score_dielectric <br />
|Dielectric constant for electrostatic term <br />
|4.0<br />
|-<br />
|fps_score_vdw_scale <br />
|Scalar multiplier of vdw energy component <br />
|1<br />
|-<br />
|fps_score_es_scale <br />
|Scalar multiplier of es energy component <br />
|1<br />
|-<br />
|fps_score_hb_scale <br />
|Scalar multiplier of hb energy component <br />
|0<br />
|-<br />
|fps_score_internal_scale <br />
|Scalar multiplier of internal energy component <br />
|0<br />
|-<br />
|fps_score_fp_vwd_scale <br />
|Scalar multiplier of vdw footprint component <br />
|0<br />
|-<br />
|fps_score_fp_es_scale <br />
|Scalar multiplier of es footprint component <br />
|0<br />
|-<br />
|fps_score_fp_hb_scale <br />
|Scalar multiplier of hb footprint component <br />
|0<br />
|-<br />
|}<br />
<br />
===Footprint Similarity Score Output Components===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
|Footprint_similarity_score<br />
|sum of the van der Waals, electostatic, and hbond footprint similarity scores<br />
|-<br />
|FPS_vdw_energy<br />
|VDW interaction between ligand and receptor<br />
|-<br />
|FPS_es_energy<br />
|ES interaction between the ligand and receptor<br />
|-<br />
|FPS_num_hbond<br />
|number of hydrogen bonds<br />
|-<br />
|FPS_vdw+es_energy<br />
|sum of the van der Waals and electrostatic components<br />
|-<br />
|FPS_vdw_fps<br />
|vdw footprint similarity score<br />
|-<br />
|FPS_es_fps<br />
|ES footprint similarity score<br />
|-<br />
|FPS_hb_fps<br />
|hbond footprint similarity score<br />
|-<br />
|FPS_vdw_fp_numres<br />
|number of residues in the receptor considered during the calculation<br />
|-<br />
|FPS_es_fp_numres<br />
|number of residues in the receptor considered during the calculation<br />
|-<br />
|FPS_hb_fp_numres<br />
|number of residues in the receptor considered during the calculation<br />
|-<br />
|}</div>Lprentishttps://ringo.ams.stonybrook.edu/index.php?title=Scoring_Functions&diff=13095Scoring Functions2020-04-14T18:26:08Z<p>Lprentis: /* MultiGrid Score Parameters */</p>
<hr />
<div>DOCK uses several types of scoring functions to discriminate among orientations and molecules. Scoring is requested using the score_molecules parameter. A large portion of scoring functions can be called through descriptor score (but not all). Those with descriptor score functionality will be denoted in bold. <br />
<br />
== Continuous/DOCK Cartesian Energy Score==<br />
Continuous scoring may be used to evaluate a ligand:receptor complex without the investment of a grid calculation, or to perform a more detailed calculation without the numerical approximation of the grid. '''Continuous score is implemented under Descriptor Score as well'''. Continuous score is a cartesian based score and can be combined with other Cartesian based scores with very little computational expense.<br />
<br />
===Continuous/DCE Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
|continuous_score_primary<br />
| Does the user want to perform continuous non-grid scoring as the primary scoring function?<br />
| no<br />
|-<br />
|continuous_score_secondary <br />
| Does the user want to perform continuous non-grid scoring as the secondary scoring function? <br />
|no<br />
|-<br />
|cont_score_rec_filename <br />
|File that contains receptor coordinates <br />
|receptor.mol2<br />
|-<br />
|cont_score_att_exp <br />
|VDW Lennard-Jones potential attractive exponent <br />
|6<br />
|-<br />
|cont_score_rep_exp <br />
|VDW Lennard-Jones potential repulsive exponent <br />
|12<br />
|-<br />
|cont_score_rep_rad_scale <br />
|Scalar multiplier of the radii for the repulsive portion of the vdw energy component only <br />
|1.0<br />
|-<br />
|cont_score_use_dist_dep_dielectric <br />
|Distance dependent dielectric switch <br />
|yes<br />
|-<br />
|cont_score_dielectric <br />
|Dielectric constant for the electrostatic term <br />
|<br />
|- <br />
|cont_score_vdw_scale <br />
|Scalar multiplier of vdw energy component <br />
|1 <br />
|-<br />
|cont_score_vdw_scale <br />
|Flag to turn off vdw portion of the scoring function when cont_score_vdw_scale=0 <br />
|yes<br />
|- <br />
|cont_score_es_scale <br />
|Scalar multiplier of electrostatic energy component <br />
|1.0 <br />
|-<br />
|cont_score_turn_off_es <br />
|Flag to turn off es portion of the scoring function when cont_score_es_scale = 0 <br />
|yes<br />
|-<br />
|}<br />
<br />
===Continuous/DCE Score Output Components===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
|Continuous-score<br />
|sum of the van der Waals and electrostatic interactions<br />
|-<br />
|Continuous_vdw_energy<br />
|VDW interaction between ligand and receptor<br />
|-<br />
|Continuous_es_energy<br />
|ES interaction between the ligand and receptor<br />
|-<br />
|}<br />
<br />
==Grid-Based Score== <br />
DOCK needs a fast scoring function to evaluate poses rapidly during growth. The energy grid is used for this. The grid stores the non-bonded Molecular Mechanics Potential of the receptor at each grid point. <br />
[[Image:Mm-equation.png|450px|center]]<br />
'''Grid can be called under descriptor score but it is suggested to not mix grid-based and cartesian space as that will dramatically increase computing time.'''<br />
===Grid Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
| grid_score_primary<br />
| Does the user want to perform grid-based energy scoring as the primary scoring function? || yes- <br />
|-<br />
| grid_score_rep_rad_scale<br />
| Scalar multiplier of the radii for the repulsive portion of the VDW energy component only when grid score is turned on || 1.0<br />
|-<br />
| grid_score_vdw_scale <br />
| Scalar multiplier of the VDW energy component || 1<br />
|-<br />
| grid_score_turn_off_vdw <br />
| A flag to turn off vdw portion of scoring function when grid score vdw scale = 0 || yes<br />
|-<br />
| grid_score_es_scale <br />
| Flag to scale up or down the es portion of the scoring function when es scale is turned on || 1<br />
|-<br />
| grid_score_turn_off_es <br />
| A flag to turn off es portion of scoring function when grid score es scale = 0 || yes<br />
|-<br />
| grid_score_grid_prefix <br />
| The prefix to the grid files containing the desired nrg/bmp grid || grid<br />
|-<br />
|}<br />
<br />
===Grid Score Output Components===<br />
These values will be printed in the header of the mol2 file post DOCK process.<br />
<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
| Grid_score<br />
| Sum of the VDW and ES interactions <br />
|-<br />
| Grid_vdw_energy<br />
| VDW interaction between the ligand grid<br />
|-<br />
| Grid_es_energy<br />
| ES interaction betweent eh ligand and grid<br />
|}<br />
<br />
==MultiGrid Score== <br />
The MultiGrid Score is similar to the Footprint Score described below, except that in the case of the Multi-Grid Score, the pair-wise interaction energies are computed over multiple grids rather than in Cartesian space. This is done to improve the tractability of FPS calculations as well as to make it simple to combine FPS and standard Grid Score. If the multiple grids are prepared as recommended than the sum of the interactions with each grid should equal the interaction of a standard DOCK grid representing the entire target. By default MultiGrid score will equal the sum of the interactions with all grids plus a FPS component generated by treating each grid as a protein residue. User defined scaling factors allow MultiGrid score to be set to equal Grid score, FPS score or any combination thereof. Generally, "important" receptor residues are identified before-hand based on the magnitude of their interaction with the reference ligand, then a unique grid is generated to represent each of those residues. Finally, a "remainder" grid is generated to represent all remaining receptor residues. The scoring function itself will then calculate intermolecular VDW and ES energies for the reference ligand and pose ligand on each of the grids (also called footprints), then it will calculate the footprint similarity using either the Standard Euclidean, Normalized Euclidean, or Pearson Correlation similarity metrics.<br />
<br />
'''MultiGrid can be called under descriptor score but it is suggested to not mix grid-based and cartesian space as that will dramatically increase computing time.'''<br />
<br />
===MultiGrid Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
| multigrid_score_primary<br />
| Does the user want to perform grid-based energy scoring as the primary scoring function? || yes- <br />
|-<br />
| multigrid_score_rep_rad_scale<br />
| Scalar multiplier of the radii for the repulsive portion of the VDW energy component only when grid score is turned on || 1.0<br />
|-<br />
| multigrid_score_vdw_scale <br />
| Scalar multiplier of the VDW energy component || 1<br />
|-<br />
| multigrid_score_es_scale <br />
| Flag to scale up or down the es portion of the scoring function when es scale is turned on || 1<br />
|-<br />
|multigrid_score_number_of_grids <br />
|Path to the reference txt file - only used when footprint reference txt is turned on. <br />
|ligand_footprint.txt<br />
|-<br />
|multigrid_score_grid_prefix0 <br />
|Provide prefixes to identify the grids. Note that the first grid starts at '0'. The last grid should be the remainder grid. This must be done for each grid. <br />
|multigrid0<br />
|-<br />
|multigrid_score_individual_rec_ensemble <br />
|Flag for individual receptor (standard) or multiple receptor (not implemented yet). <br />
|no<br />
|-<br />
|multigrid_score_weights_text <br />
|Flag for providing a textfile as input for the reference footprint. <br />
|no<br />
|-<br />
|multigrid_score_footprint_text <br />
|Name of the reference footprint input text file, when multigrid_score_weight_text is turned on. <br />
|reference.txt<br />
|-<br />
|multigrid_score_fp_ref_mol <br />
|Flag for providing a MOL2 as input for the reference footprint. <br />
|no<br />
|-<br />
|multigrid_score_footprint_ref <br />
|Name of the reference footprint input MOL2 file, when multigrid_score_fp_ref_mol is turned on. <br />
|reference.mol2<br />
|-<br />
|multigrid_score_foot_compare_type <br />
|Footprint similarity calculation methods (Options: Euclidean, Pearson). If Pearson, the correlation coefficient as the metric to compare the footprints. When the value is 1 then there is perfect agreement between the two footprints. WHen the value is 0 then there is poor agreement between the two footprints. If Euclidean, the Euclidean distance as the metric to compare the footprints. When the value is 0 then there is perfect agreement btween the two footprints. As the agreement gets worse between the two footprints the value increases. <br />
|Euclidean<br />
|-<br />
|multigrid_score_normalize_foot <br />
|normalization is used only with Euclidean distance. <br />
|no<br />
|-<br />
|multigrid_score_vdw_euc_scale <br />
|Scaling factor for VDW term. when using euclidean <br />
|1.0<br />
|-<br />
|multigrid_score_es_euc_scale <br />
|Scaling factor for ES term when using euclidean <br />
|1.0<br />
|-<br />
|multigrid_score_vdw_norm_scale <br />
|Scaling factor for VDW term. euclidean and normalize <br />
|10.0<br />
|-<br />
|multigrid_score_es_norm_scale <br />
|Scaling factor for ES term. Flags if using Pearson Correlation similarity metric for footprint comparison. <br />
|10.0<br />
|-<br />
|multigrid_score_vdw_cor_scale <br />
|Scaling factor for VDW term <br />
|(-10.0)<br />
|-<br />
|multigrid_score_es_cor_scale <br />
|Scaling factor for ES term <br />
|(-10.0)<br />
|-<br />
|}<br />
<br />
===MultiGrid Score Output Components===<br />
These values will be printed in the header of the mol2 file post DOCK process.<br />
<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
| Grid_score<br />
| Sum of the VDW and ES interactions <br />
|-<br />
| Grid_vdw_energy<br />
| VDW interaction between the ligand grid<br />
|-<br />
| Grid_es_energy<br />
| ES interaction betweent eh ligand and grid<br />
|}<br />
<br />
==Footprint Similarity Score==<br />
The Footprint Similarity Score is a scoring function that calculates intermolecular hydrogen bonds and footprint comparisons, in addition to standard intermolecular energies (VDW and ES). <br />
<br />
Intermolecular Energies (VDW, ES) are calculated the same way as in Continuous Score.<br />
<br />
A geometric definition of Hydrogen bonds is employed. We define 3 atoms XD, HD, and XA as the heavy atom donor, donated hydrogen, and heavy atom acceptor, respectively. There is a hydrogen bond present if the following two conditions are met:<br />
<br />
# The distance between HD and XA is less than or equal to 2.5 angstroms;<br />
# The angle defined by XD, HD, and XA is between 120 and 180 degrees.<br />
<br />
Footprints are a per-residue decomposition of interactions between the ligand and the receptor. This can be performed for all three terms VDW, ES, HB.<br />
Two footprints can be compared in three ways: Standard Euclidean, Normalized Euclidean, Pearson Correlation.<br />
<br />
Footprints are used to gauge how similar two poses or two molecules are to one-another. For applications to virtual screening applications a reference is required.<br />
<br />
There are to choices for a reference:<br />
<br />
# One can give a mol2 file containing a reference molecule, and footprints will be calculated.<br />
# One can pass a text file containing VDW, ES, and H-bond footprints. <br />
There are different choices for selection of residues:<br />
<br />
# All residues.<br />
# Residues chosen using a threshold (union of the sets of reference and pose). The VDW, ES, and HB footprints may have different residues chosen in this case.<br />
# Selected residues.<br />
<br />
Note that for (2) and (3) the remaining residue interaction may be placed in a remainder value included in the footprint.<br />
<br />
'''Footprint Similarity Score can be called under Descriptor Score.'''<br />
<br />
===Footprint Similarity Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
|footprint_similarity_score_primary <br />
|Flag to perform footprint scoring as the primary scoring function <br />
|no<br />
|-<br />
|footprint_similarity_score_secondary <br />
|Flag to perform footprint scoring as the secondary scoring function. <br />
|no<br />
|-<br />
|fps_score_use_footprint_reference_mol2 <br />
|Use a molecule to calculate footprint reference. <br />
|no<br />
|-<br />
|fps_score_footprint_reference_mol2_filename <br />
|Path to the reference mol2 file - only used when footprint reference mol2 is turned on. <br />
|ligand_footprint.mol2<br />
|-<br />
|fps_score_use_footprint_reference_txt <br />
|Use a pre-calculated footprint reference in text format. <br />
|no<br />
|-<br />
|fps_score_footprint_reference_txt_filename <br />
|Path to the reference txt file - only used when footprint reference txt is turned on. <br />
|ligand_footprint.txt<br />
|-<br />
|fps_score_foot_compare_type <br />
|Footprint similarity calculation methods (Options: Euclidean, Pearson). If Pearson, the correlation coefficient as the metric to compare the footprints. When the value is 1 then there is perfect agreement between the two footprints. WHen the value is 0 then there is poor agreement between the two footprints. If Euclidean, the Euclidean distance as the metric to compare the footprints. When the value is 0 then there is perfect agreement btween the two footprints. As the agreement gets worse between the two footprints the value increases. <br />
|Euclidean<br />
|-<br />
|fps_score_normalize_foot <br />
|normalization is used only with Euclidean distance. <br />
|no<br />
|-<br />
|fps_score_foot_comp_all_residue <br />
|If yes all residues are used for calculating the footprint. <br />
|yes<br />
|-<br />
|fps_score_choose_foot_range_type <br />
|User can use to determine the type of the range of the footprint by either specifying a residue range or defining a threshold. If specify_range, the user chooses to use a residue range and all footprints will be evaluated only on this residue range. First residue id = 1 not 0. If threshold, the user chose to use a residue range that is defined by only residues that have magnitudes that exceed the specified thresholds. (Options: specify_range, threshold) <br />
|specify_range<br />
|-<br />
|fps_score_vdw_threshold <br />
|Specify threshold for van der Waals energy, when threshold is turned on. <br />
|1<br />
|-<br />
|fps_score_es_threshold <br />
|Specify threshold for electrostatic energy, when threshold is turned on. <br />
|1<br />
|-<br />
|fps_score_hb_threshold <br />
|specify threshold for hydrogen bonds (integers). 0.5 means that all none zeros are used, when threshold is turned on. <br />
|0.5<br />
|-<br />
|fps_score_use_remainder <br />
|Interaction remainder is all remaining residues not included individually <br />
|yes<br />
|-<br />
|fps_score_rec_filename <br />
|File that contains receptor coordinates <br />
|receptor.mol2<br />
|-<br />
|fps_score_att_exp <br />
|VDW Lennard-Jones potential attractive exponent <br />
|6<br />
|-<br />
|fps_score_rep_exp <br />
|VDW Lennard-Jones potential repulsive exponent <br />
|12<br />
|-<br />
|fps_score_rep_rad_scale <br />
|Scalar multiplier of the radii for the repulsive portion of the VDW energy component ONLY <br />
|1<br />
|-<br />
|fps_score_use_distance_dependent_dielectric <br />
|Distance dependent dielectric switch <br />
|yes<br />
|-<br />
|fps_score_dielectric <br />
|Dielectric constant for electrostatic term <br />
|4.0<br />
|-<br />
|fps_score_vdw_scale <br />
|Scalar multiplier of vdw energy component <br />
|1<br />
|-<br />
|fps_score_es_scale <br />
|Scalar multiplier of es energy component <br />
|1<br />
|-<br />
|fps_score_hb_scale <br />
|Scalar multiplier of hb energy component <br />
|0<br />
|-<br />
|fps_score_internal_scale <br />
|Scalar multiplier of internal energy component <br />
|0<br />
|-<br />
|fps_score_fp_vwd_scale <br />
|Scalar multiplier of vdw footprint component <br />
|0<br />
|-<br />
|fps_score_fp_es_scale <br />
|Scalar multiplier of es footprint component <br />
|0<br />
|-<br />
|fps_score_fp_hb_scale <br />
|Scalar multiplier of hb footprint component <br />
|0<br />
|-<br />
|}<br />
<br />
===Footprint Similarity Score Output Components===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
|Footprint_similarity_score<br />
|sum of the van der Waals, electostatic, and hbond footprint similarity scores<br />
|-<br />
|FPS_vdw_energy<br />
|VDW interaction between ligand and receptor<br />
|-<br />
|FPS_es_energy<br />
|ES interaction between the ligand and receptor<br />
|-<br />
|FPS_num_hbond<br />
|number of hydrogen bonds<br />
|-<br />
|FPS_vdw+es_energy<br />
|sum of the van der Waals and electrostatic components<br />
|-<br />
|FPS_vdw_fps<br />
|vdw footprint similarity score<br />
|-<br />
|FPS_es_fps<br />
|ES footprint similarity score<br />
|-<br />
|FPS_hb_fps<br />
|hbond footprint similarity score<br />
|-<br />
|FPS_vdw_fp_numres<br />
|number of residues in the receptor considered during the calculation<br />
|-<br />
|FPS_es_fp_numres<br />
|number of residues in the receptor considered during the calculation<br />
|-<br />
|FPS_hb_fp_numres<br />
|number of residues in the receptor considered during the calculation<br />
|-<br />
|}</div>Lprentishttps://ringo.ams.stonybrook.edu/index.php?title=Scoring_Functions&diff=13094Scoring Functions2020-04-14T18:25:45Z<p>Lprentis: /* MultiGrid Score Parameters */</p>
<hr />
<div>DOCK uses several types of scoring functions to discriminate among orientations and molecules. Scoring is requested using the score_molecules parameter. A large portion of scoring functions can be called through descriptor score (but not all). Those with descriptor score functionality will be denoted in bold. <br />
<br />
== Continuous/DOCK Cartesian Energy Score==<br />
Continuous scoring may be used to evaluate a ligand:receptor complex without the investment of a grid calculation, or to perform a more detailed calculation without the numerical approximation of the grid. '''Continuous score is implemented under Descriptor Score as well'''. Continuous score is a cartesian based score and can be combined with other Cartesian based scores with very little computational expense.<br />
<br />
===Continuous/DCE Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
|continuous_score_primary<br />
| Does the user want to perform continuous non-grid scoring as the primary scoring function?<br />
| no<br />
|-<br />
|continuous_score_secondary <br />
| Does the user want to perform continuous non-grid scoring as the secondary scoring function? <br />
|no<br />
|-<br />
|cont_score_rec_filename <br />
|File that contains receptor coordinates <br />
|receptor.mol2<br />
|-<br />
|cont_score_att_exp <br />
|VDW Lennard-Jones potential attractive exponent <br />
|6<br />
|-<br />
|cont_score_rep_exp <br />
|VDW Lennard-Jones potential repulsive exponent <br />
|12<br />
|-<br />
|cont_score_rep_rad_scale <br />
|Scalar multiplier of the radii for the repulsive portion of the vdw energy component only <br />
|1.0<br />
|-<br />
|cont_score_use_dist_dep_dielectric <br />
|Distance dependent dielectric switch <br />
|yes<br />
|-<br />
|cont_score_dielectric <br />
|Dielectric constant for the electrostatic term <br />
|<br />
|- <br />
|cont_score_vdw_scale <br />
|Scalar multiplier of vdw energy component <br />
|1 <br />
|-<br />
|cont_score_vdw_scale <br />
|Flag to turn off vdw portion of the scoring function when cont_score_vdw_scale=0 <br />
|yes<br />
|- <br />
|cont_score_es_scale <br />
|Scalar multiplier of electrostatic energy component <br />
|1.0 <br />
|-<br />
|cont_score_turn_off_es <br />
|Flag to turn off es portion of the scoring function when cont_score_es_scale = 0 <br />
|yes<br />
|-<br />
|}<br />
<br />
===Continuous/DCE Score Output Components===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
|Continuous-score<br />
|sum of the van der Waals and electrostatic interactions<br />
|-<br />
|Continuous_vdw_energy<br />
|VDW interaction between ligand and receptor<br />
|-<br />
|Continuous_es_energy<br />
|ES interaction between the ligand and receptor<br />
|-<br />
|}<br />
<br />
==Grid-Based Score== <br />
DOCK needs a fast scoring function to evaluate poses rapidly during growth. The energy grid is used for this. The grid stores the non-bonded Molecular Mechanics Potential of the receptor at each grid point. <br />
[[Image:Mm-equation.png|450px|center]]<br />
'''Grid can be called under descriptor score but it is suggested to not mix grid-based and cartesian space as that will dramatically increase computing time.'''<br />
===Grid Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
| grid_score_primary<br />
| Does the user want to perform grid-based energy scoring as the primary scoring function? || yes- <br />
|-<br />
| grid_score_rep_rad_scale<br />
| Scalar multiplier of the radii for the repulsive portion of the VDW energy component only when grid score is turned on || 1.0<br />
|-<br />
| grid_score_vdw_scale <br />
| Scalar multiplier of the VDW energy component || 1<br />
|-<br />
| grid_score_turn_off_vdw <br />
| A flag to turn off vdw portion of scoring function when grid score vdw scale = 0 || yes<br />
|-<br />
| grid_score_es_scale <br />
| Flag to scale up or down the es portion of the scoring function when es scale is turned on || 1<br />
|-<br />
| grid_score_turn_off_es <br />
| A flag to turn off es portion of scoring function when grid score es scale = 0 || yes<br />
|-<br />
| grid_score_grid_prefix <br />
| The prefix to the grid files containing the desired nrg/bmp grid || grid<br />
|-<br />
|}<br />
<br />
===Grid Score Output Components===<br />
These values will be printed in the header of the mol2 file post DOCK process.<br />
<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
| Grid_score<br />
| Sum of the VDW and ES interactions <br />
|-<br />
| Grid_vdw_energy<br />
| VDW interaction between the ligand grid<br />
|-<br />
| Grid_es_energy<br />
| ES interaction betweent eh ligand and grid<br />
|}<br />
<br />
==MultiGrid Score== <br />
The MultiGrid Score is similar to the Footprint Score described below, except that in the case of the Multi-Grid Score, the pair-wise interaction energies are computed over multiple grids rather than in Cartesian space. This is done to improve the tractability of FPS calculations as well as to make it simple to combine FPS and standard Grid Score. If the multiple grids are prepared as recommended than the sum of the interactions with each grid should equal the interaction of a standard DOCK grid representing the entire target. By default MultiGrid score will equal the sum of the interactions with all grids plus a FPS component generated by treating each grid as a protein residue. User defined scaling factors allow MultiGrid score to be set to equal Grid score, FPS score or any combination thereof. Generally, "important" receptor residues are identified before-hand based on the magnitude of their interaction with the reference ligand, then a unique grid is generated to represent each of those residues. Finally, a "remainder" grid is generated to represent all remaining receptor residues. The scoring function itself will then calculate intermolecular VDW and ES energies for the reference ligand and pose ligand on each of the grids (also called footprints), then it will calculate the footprint similarity using either the Standard Euclidean, Normalized Euclidean, or Pearson Correlation similarity metrics.<br />
<br />
'''MultiGrid can be called under descriptor score but it is suggested to not mix grid-based and cartesian space as that will dramatically increase computing time.'''<br />
<br />
===MultiGrid Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
| multigrid_score_primary<br />
| Does the user want to perform grid-based energy scoring as the primary scoring function? || yes- <br />
|-<br />
| multigrid_score_rep_rad_scale<br />
| Scalar multiplier of the radii for the repulsive portion of the VDW energy component only when grid score is turned on || 1.0<br />
|-<br />
| multigrid_score_vdw_scale <br />
| Scalar multiplier of the VDW energy component || 1<br />
|-<br />
| multigrid_score_es_scale <br />
| Flag to scale up or down the es portion of the scoring function when es scale is turned on || 1<br />
|-<br />
|multigrid_score_number_of_grids <br />
|Path to the reference txt file - only used when footprint reference txt is turned on. <br />
|ligand_footprint.txt<br />
|-<br />
|multigrid_score_grid_prefix0 <br />
|Provide prefixes to identify the grids. Note that the first grid starts at '0'. The last grid should be the remainder grid. This must be done for each grid. <br />
|multigrid0<br />
|-<br />
|multigrid_score_individual_rec_ensemble <br />
|Flag for individual receptor (standard) or multiple receptor (not implemented yet). <br />
|no<br />
|-<br />
|multigrid_score_weights_text <br />
|Flag for providing a textfile as input for the reference footprint. <br />
|no<br />
|-<br />
|multigrid_score_footprint_text <br />
|Name of the reference footprint input text file, when multigrid_score_weight_text is turned on. <br />
|reference.txt<br />
|-<br />
|multigrid_score_fp_ref_mol <br />
|Flag for providing a MOL2 as input for the reference footprint. <br />
|no<br />
|-<br />
|multigrid_score_footprint_ref <br />
|Name of the reference footprint input MOL2 file, when multigrid_score_fp_ref_mol is turned on. <br />
|reference.mol2<br />
|-<br />
|multigrid_score_foot_compare_type <br />
|Footprint similarity calculation methods (Options: Euclidean, Pearson). If Pearson, the correlation coefficient as the metric to compare the footprints. When the value is 1 then there is perfect agreement between the two footprints. WHen the value is 0 then there is poor agreement between the two footprints. If Euclidean, the Euclidean distance as the metric to compare the footprints. When the value is 0 then there is perfect agreement btween the two footprints. As the agreement gets worse between the two footprints the value increases. <br />
|Euclidean<br />
|-<br />
|multigrid_score_normalize_foot <br />
|normalization is used only with Euclidean distance. <br />
|no<br />
|-<br />
|multigrid_score_vdw_euc_scale <br />
|Scaling factor for VDW term. when using euclidean <br />
|1.0<br />
|-<br />
|multigrid_score_es_euc_scale <br />
|Scaling factor for ES term when using euclidean <br />
|1.0<br />
|-<br />
|multigrid_score_vdw_norm_scale <br />
|Scaling factor for VDW term. euclidean and normalize <br />
|10.0<br />
|-<br />
|multigrid_score_es_norm_scale <br />
|Scaling factor for ES term. Flags if using Pearson Correlation similarity metric for footprint comparison. <br />
|10.0<br />
|-<br />
|multigrid_score_vdw_cor_scale <br />
|Scaling factor for VDW term <br />
|\-10.0<br />
|-<br />
|multigrid_score_es_cor_scale <br />
|Scaling factor for ES term <br />
|\-10.0<br />
|-<br />
|}<br />
<br />
===MultiGrid Score Output Components===<br />
These values will be printed in the header of the mol2 file post DOCK process.<br />
<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
| Grid_score<br />
| Sum of the VDW and ES interactions <br />
|-<br />
| Grid_vdw_energy<br />
| VDW interaction between the ligand grid<br />
|-<br />
| Grid_es_energy<br />
| ES interaction betweent eh ligand and grid<br />
|}<br />
<br />
==Footprint Similarity Score==<br />
The Footprint Similarity Score is a scoring function that calculates intermolecular hydrogen bonds and footprint comparisons, in addition to standard intermolecular energies (VDW and ES). <br />
<br />
Intermolecular Energies (VDW, ES) are calculated the same way as in Continuous Score.<br />
<br />
A geometric definition of Hydrogen bonds is employed. We define 3 atoms XD, HD, and XA as the heavy atom donor, donated hydrogen, and heavy atom acceptor, respectively. There is a hydrogen bond present if the following two conditions are met:<br />
<br />
# The distance between HD and XA is less than or equal to 2.5 angstroms;<br />
# The angle defined by XD, HD, and XA is between 120 and 180 degrees.<br />
<br />
Footprints are a per-residue decomposition of interactions between the ligand and the receptor. This can be performed for all three terms VDW, ES, HB.<br />
Two footprints can be compared in three ways: Standard Euclidean, Normalized Euclidean, Pearson Correlation.<br />
<br />
Footprints are used to gauge how similar two poses or two molecules are to one-another. For applications to virtual screening applications a reference is required.<br />
<br />
There are to choices for a reference:<br />
<br />
# One can give a mol2 file containing a reference molecule, and footprints will be calculated.<br />
# One can pass a text file containing VDW, ES, and H-bond footprints. <br />
There are different choices for selection of residues:<br />
<br />
# All residues.<br />
# Residues chosen using a threshold (union of the sets of reference and pose). The VDW, ES, and HB footprints may have different residues chosen in this case.<br />
# Selected residues.<br />
<br />
Note that for (2) and (3) the remaining residue interaction may be placed in a remainder value included in the footprint.<br />
<br />
'''Footprint Similarity Score can be called under Descriptor Score.'''<br />
<br />
===Footprint Similarity Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
|footprint_similarity_score_primary <br />
|Flag to perform footprint scoring as the primary scoring function <br />
|no<br />
|-<br />
|footprint_similarity_score_secondary <br />
|Flag to perform footprint scoring as the secondary scoring function. <br />
|no<br />
|-<br />
|fps_score_use_footprint_reference_mol2 <br />
|Use a molecule to calculate footprint reference. <br />
|no<br />
|-<br />
|fps_score_footprint_reference_mol2_filename <br />
|Path to the reference mol2 file - only used when footprint reference mol2 is turned on. <br />
|ligand_footprint.mol2<br />
|-<br />
|fps_score_use_footprint_reference_txt <br />
|Use a pre-calculated footprint reference in text format. <br />
|no<br />
|-<br />
|fps_score_footprint_reference_txt_filename <br />
|Path to the reference txt file - only used when footprint reference txt is turned on. <br />
|ligand_footprint.txt<br />
|-<br />
|fps_score_foot_compare_type <br />
|Footprint similarity calculation methods (Options: Euclidean, Pearson). If Pearson, the correlation coefficient as the metric to compare the footprints. When the value is 1 then there is perfect agreement between the two footprints. WHen the value is 0 then there is poor agreement between the two footprints. If Euclidean, the Euclidean distance as the metric to compare the footprints. When the value is 0 then there is perfect agreement btween the two footprints. As the agreement gets worse between the two footprints the value increases. <br />
|Euclidean<br />
|-<br />
|fps_score_normalize_foot <br />
|normalization is used only with Euclidean distance. <br />
|no<br />
|-<br />
|fps_score_foot_comp_all_residue <br />
|If yes all residues are used for calculating the footprint. <br />
|yes<br />
|-<br />
|fps_score_choose_foot_range_type <br />
|User can use to determine the type of the range of the footprint by either specifying a residue range or defining a threshold. If specify_range, the user chooses to use a residue range and all footprints will be evaluated only on this residue range. First residue id = 1 not 0. If threshold, the user chose to use a residue range that is defined by only residues that have magnitudes that exceed the specified thresholds. (Options: specify_range, threshold) <br />
|specify_range<br />
|-<br />
|fps_score_vdw_threshold <br />
|Specify threshold for van der Waals energy, when threshold is turned on. <br />
|1<br />
|-<br />
|fps_score_es_threshold <br />
|Specify threshold for electrostatic energy, when threshold is turned on. <br />
|1<br />
|-<br />
|fps_score_hb_threshold <br />
|specify threshold for hydrogen bonds (integers). 0.5 means that all none zeros are used, when threshold is turned on. <br />
|0.5<br />
|-<br />
|fps_score_use_remainder <br />
|Interaction remainder is all remaining residues not included individually <br />
|yes<br />
|-<br />
|fps_score_rec_filename <br />
|File that contains receptor coordinates <br />
|receptor.mol2<br />
|-<br />
|fps_score_att_exp <br />
|VDW Lennard-Jones potential attractive exponent <br />
|6<br />
|-<br />
|fps_score_rep_exp <br />
|VDW Lennard-Jones potential repulsive exponent <br />
|12<br />
|-<br />
|fps_score_rep_rad_scale <br />
|Scalar multiplier of the radii for the repulsive portion of the VDW energy component ONLY <br />
|1<br />
|-<br />
|fps_score_use_distance_dependent_dielectric <br />
|Distance dependent dielectric switch <br />
|yes<br />
|-<br />
|fps_score_dielectric <br />
|Dielectric constant for electrostatic term <br />
|4.0<br />
|-<br />
|fps_score_vdw_scale <br />
|Scalar multiplier of vdw energy component <br />
|1<br />
|-<br />
|fps_score_es_scale <br />
|Scalar multiplier of es energy component <br />
|1<br />
|-<br />
|fps_score_hb_scale <br />
|Scalar multiplier of hb energy component <br />
|0<br />
|-<br />
|fps_score_internal_scale <br />
|Scalar multiplier of internal energy component <br />
|0<br />
|-<br />
|fps_score_fp_vwd_scale <br />
|Scalar multiplier of vdw footprint component <br />
|0<br />
|-<br />
|fps_score_fp_es_scale <br />
|Scalar multiplier of es footprint component <br />
|0<br />
|-<br />
|fps_score_fp_hb_scale <br />
|Scalar multiplier of hb footprint component <br />
|0<br />
|-<br />
|}<br />
<br />
===Footprint Similarity Score Output Components===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
|Footprint_similarity_score<br />
|sum of the van der Waals, electostatic, and hbond footprint similarity scores<br />
|-<br />
|FPS_vdw_energy<br />
|VDW interaction between ligand and receptor<br />
|-<br />
|FPS_es_energy<br />
|ES interaction between the ligand and receptor<br />
|-<br />
|FPS_num_hbond<br />
|number of hydrogen bonds<br />
|-<br />
|FPS_vdw+es_energy<br />
|sum of the van der Waals and electrostatic components<br />
|-<br />
|FPS_vdw_fps<br />
|vdw footprint similarity score<br />
|-<br />
|FPS_es_fps<br />
|ES footprint similarity score<br />
|-<br />
|FPS_hb_fps<br />
|hbond footprint similarity score<br />
|-<br />
|FPS_vdw_fp_numres<br />
|number of residues in the receptor considered during the calculation<br />
|-<br />
|FPS_es_fp_numres<br />
|number of residues in the receptor considered during the calculation<br />
|-<br />
|FPS_hb_fp_numres<br />
|number of residues in the receptor considered during the calculation<br />
|-<br />
|}</div>Lprentishttps://ringo.ams.stonybrook.edu/index.php?title=Scoring_Functions&diff=13093Scoring Functions2020-04-14T18:25:15Z<p>Lprentis: /* MultiGrid Score */</p>
<hr />
<div>DOCK uses several types of scoring functions to discriminate among orientations and molecules. Scoring is requested using the score_molecules parameter. A large portion of scoring functions can be called through descriptor score (but not all). Those with descriptor score functionality will be denoted in bold. <br />
<br />
== Continuous/DOCK Cartesian Energy Score==<br />
Continuous scoring may be used to evaluate a ligand:receptor complex without the investment of a grid calculation, or to perform a more detailed calculation without the numerical approximation of the grid. '''Continuous score is implemented under Descriptor Score as well'''. Continuous score is a cartesian based score and can be combined with other Cartesian based scores with very little computational expense.<br />
<br />
===Continuous/DCE Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
|continuous_score_primary<br />
| Does the user want to perform continuous non-grid scoring as the primary scoring function?<br />
| no<br />
|-<br />
|continuous_score_secondary <br />
| Does the user want to perform continuous non-grid scoring as the secondary scoring function? <br />
|no<br />
|-<br />
|cont_score_rec_filename <br />
|File that contains receptor coordinates <br />
|receptor.mol2<br />
|-<br />
|cont_score_att_exp <br />
|VDW Lennard-Jones potential attractive exponent <br />
|6<br />
|-<br />
|cont_score_rep_exp <br />
|VDW Lennard-Jones potential repulsive exponent <br />
|12<br />
|-<br />
|cont_score_rep_rad_scale <br />
|Scalar multiplier of the radii for the repulsive portion of the vdw energy component only <br />
|1.0<br />
|-<br />
|cont_score_use_dist_dep_dielectric <br />
|Distance dependent dielectric switch <br />
|yes<br />
|-<br />
|cont_score_dielectric <br />
|Dielectric constant for the electrostatic term <br />
|<br />
|- <br />
|cont_score_vdw_scale <br />
|Scalar multiplier of vdw energy component <br />
|1 <br />
|-<br />
|cont_score_vdw_scale <br />
|Flag to turn off vdw portion of the scoring function when cont_score_vdw_scale=0 <br />
|yes<br />
|- <br />
|cont_score_es_scale <br />
|Scalar multiplier of electrostatic energy component <br />
|1.0 <br />
|-<br />
|cont_score_turn_off_es <br />
|Flag to turn off es portion of the scoring function when cont_score_es_scale = 0 <br />
|yes<br />
|-<br />
|}<br />
<br />
===Continuous/DCE Score Output Components===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
|Continuous-score<br />
|sum of the van der Waals and electrostatic interactions<br />
|-<br />
|Continuous_vdw_energy<br />
|VDW interaction between ligand and receptor<br />
|-<br />
|Continuous_es_energy<br />
|ES interaction between the ligand and receptor<br />
|-<br />
|}<br />
<br />
==Grid-Based Score== <br />
DOCK needs a fast scoring function to evaluate poses rapidly during growth. The energy grid is used for this. The grid stores the non-bonded Molecular Mechanics Potential of the receptor at each grid point. <br />
[[Image:Mm-equation.png|450px|center]]<br />
'''Grid can be called under descriptor score but it is suggested to not mix grid-based and cartesian space as that will dramatically increase computing time.'''<br />
===Grid Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
| grid_score_primary<br />
| Does the user want to perform grid-based energy scoring as the primary scoring function? || yes- <br />
|-<br />
| grid_score_rep_rad_scale<br />
| Scalar multiplier of the radii for the repulsive portion of the VDW energy component only when grid score is turned on || 1.0<br />
|-<br />
| grid_score_vdw_scale <br />
| Scalar multiplier of the VDW energy component || 1<br />
|-<br />
| grid_score_turn_off_vdw <br />
| A flag to turn off vdw portion of scoring function when grid score vdw scale = 0 || yes<br />
|-<br />
| grid_score_es_scale <br />
| Flag to scale up or down the es portion of the scoring function when es scale is turned on || 1<br />
|-<br />
| grid_score_turn_off_es <br />
| A flag to turn off es portion of scoring function when grid score es scale = 0 || yes<br />
|-<br />
| grid_score_grid_prefix <br />
| The prefix to the grid files containing the desired nrg/bmp grid || grid<br />
|-<br />
|}<br />
<br />
===Grid Score Output Components===<br />
These values will be printed in the header of the mol2 file post DOCK process.<br />
<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
| Grid_score<br />
| Sum of the VDW and ES interactions <br />
|-<br />
| Grid_vdw_energy<br />
| VDW interaction between the ligand grid<br />
|-<br />
| Grid_es_energy<br />
| ES interaction betweent eh ligand and grid<br />
|}<br />
<br />
==MultiGrid Score== <br />
The MultiGrid Score is similar to the Footprint Score described below, except that in the case of the Multi-Grid Score, the pair-wise interaction energies are computed over multiple grids rather than in Cartesian space. This is done to improve the tractability of FPS calculations as well as to make it simple to combine FPS and standard Grid Score. If the multiple grids are prepared as recommended than the sum of the interactions with each grid should equal the interaction of a standard DOCK grid representing the entire target. By default MultiGrid score will equal the sum of the interactions with all grids plus a FPS component generated by treating each grid as a protein residue. User defined scaling factors allow MultiGrid score to be set to equal Grid score, FPS score or any combination thereof. Generally, "important" receptor residues are identified before-hand based on the magnitude of their interaction with the reference ligand, then a unique grid is generated to represent each of those residues. Finally, a "remainder" grid is generated to represent all remaining receptor residues. The scoring function itself will then calculate intermolecular VDW and ES energies for the reference ligand and pose ligand on each of the grids (also called footprints), then it will calculate the footprint similarity using either the Standard Euclidean, Normalized Euclidean, or Pearson Correlation similarity metrics.<br />
<br />
'''MultiGrid can be called under descriptor score but it is suggested to not mix grid-based and cartesian space as that will dramatically increase computing time.'''<br />
<br />
===MultiGrid Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
| multigrid_score_primary<br />
| Does the user want to perform grid-based energy scoring as the primary scoring function? || yes- <br />
|-<br />
| multigrid_score_rep_rad_scale<br />
| Scalar multiplier of the radii for the repulsive portion of the VDW energy component only when grid score is turned on || 1.0<br />
|-<br />
| multigrid_score_vdw_scale <br />
| Scalar multiplier of the VDW energy component || 1<br />
|-<br />
| multigrid_score_es_scale <br />
| Flag to scale up or down the es portion of the scoring function when es scale is turned on || 1<br />
|-<br />
|multigrid_score_number_of_grids <br />
|Path to the reference txt file - only used when footprint reference txt is turned on. <br />
|ligand_footprint.txt<br />
|-<br />
|multigrid_score_grid_prefix0 <br />
|Provide prefixes to identify the grids. Note that the first grid starts at '0'. The last grid should be the remainder grid. This must be done for each grid. <br />
|multigrid0<br />
|-<br />
|multigrid_score_individual_rec_ensemble <br />
|Flag for individual receptor (standard) or multiple receptor (not implemented yet). <br />
|no<br />
|-<br />
|multigrid_score_weights_text <br />
|Flag for providing a textfile as input for the reference footprint. <br />
|no<br />
|-<br />
|multigrid_score_footprint_text <br />
|Name of the reference footprint input text file, when multigrid_score_weight_text is turned on. <br />
|reference.txt<br />
|-<br />
|multigrid_score_fp_ref_mol <br />
|Flag for providing a MOL2 as input for the reference footprint. <br />
|no<br />
|-<br />
|multigrid_score_footprint_ref <br />
|Name of the reference footprint input MOL2 file, when multigrid_score_fp_ref_mol is turned on. <br />
|reference.mol2<br />
|-<br />
|multigrid_score_foot_compare_type <br />
|Footprint similarity calculation methods (Options: Euclidean, Pearson). If Pearson, the correlation coefficient as the metric to compare the footprints. When the value is 1 then there is perfect agreement between the two footprints. WHen the value is 0 then there is poor agreement between the two footprints. If Euclidean, the Euclidean distance as the metric to compare the footprints. When the value is 0 then there is perfect agreement btween the two footprints. As the agreement gets worse between the two footprints the value increases. <br />
|Euclidean<br />
|-<br />
|multigrid_score_normalize_foot <br />
|normalization is used only with Euclidean distance. <br />
|no<br />
|-<br />
|multigrid_score_vdw_euc_scale <br />
|Scaling factor for VDW term. when using euclidean <br />
|1.0<br />
|-<br />
|multigrid_score_es_euc_scale <br />
|Scaling factor for ES term when using euclidean <br />
|1.0<br />
|-<br />
|multigrid_score_vdw_norm_scale <br />
|Scaling factor for VDW term. euclidean and normalize <br />
|10.0<br />
|-<br />
|multigrid_score_es_norm_scale <br />
|Scaling factor for ES term. Flags if using Pearson Correlation similarity metric for footprint comparison. <br />
|10.0<br />
|-<br />
|multigrid_score_vdw_cor_scale <br />
|Scaling factor for VDW term <br />
|-10.0<br />
|-<br />
|multigrid_score_es_cor_scale <br />
|Scaling factor for ES term <br />
|-10.0<br />
|-<br />
|}<br />
<br />
===MultiGrid Score Output Components===<br />
These values will be printed in the header of the mol2 file post DOCK process.<br />
<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
| Grid_score<br />
| Sum of the VDW and ES interactions <br />
|-<br />
| Grid_vdw_energy<br />
| VDW interaction between the ligand grid<br />
|-<br />
| Grid_es_energy<br />
| ES interaction betweent eh ligand and grid<br />
|}<br />
<br />
==Footprint Similarity Score==<br />
The Footprint Similarity Score is a scoring function that calculates intermolecular hydrogen bonds and footprint comparisons, in addition to standard intermolecular energies (VDW and ES). <br />
<br />
Intermolecular Energies (VDW, ES) are calculated the same way as in Continuous Score.<br />
<br />
A geometric definition of Hydrogen bonds is employed. We define 3 atoms XD, HD, and XA as the heavy atom donor, donated hydrogen, and heavy atom acceptor, respectively. There is a hydrogen bond present if the following two conditions are met:<br />
<br />
# The distance between HD and XA is less than or equal to 2.5 angstroms;<br />
# The angle defined by XD, HD, and XA is between 120 and 180 degrees.<br />
<br />
Footprints are a per-residue decomposition of interactions between the ligand and the receptor. This can be performed for all three terms VDW, ES, HB.<br />
Two footprints can be compared in three ways: Standard Euclidean, Normalized Euclidean, Pearson Correlation.<br />
<br />
Footprints are used to gauge how similar two poses or two molecules are to one-another. For applications to virtual screening applications a reference is required.<br />
<br />
There are to choices for a reference:<br />
<br />
# One can give a mol2 file containing a reference molecule, and footprints will be calculated.<br />
# One can pass a text file containing VDW, ES, and H-bond footprints. <br />
There are different choices for selection of residues:<br />
<br />
# All residues.<br />
# Residues chosen using a threshold (union of the sets of reference and pose). The VDW, ES, and HB footprints may have different residues chosen in this case.<br />
# Selected residues.<br />
<br />
Note that for (2) and (3) the remaining residue interaction may be placed in a remainder value included in the footprint.<br />
<br />
'''Footprint Similarity Score can be called under Descriptor Score.'''<br />
<br />
===Footprint Similarity Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
|footprint_similarity_score_primary <br />
|Flag to perform footprint scoring as the primary scoring function <br />
|no<br />
|-<br />
|footprint_similarity_score_secondary <br />
|Flag to perform footprint scoring as the secondary scoring function. <br />
|no<br />
|-<br />
|fps_score_use_footprint_reference_mol2 <br />
|Use a molecule to calculate footprint reference. <br />
|no<br />
|-<br />
|fps_score_footprint_reference_mol2_filename <br />
|Path to the reference mol2 file - only used when footprint reference mol2 is turned on. <br />
|ligand_footprint.mol2<br />
|-<br />
|fps_score_use_footprint_reference_txt <br />
|Use a pre-calculated footprint reference in text format. <br />
|no<br />
|-<br />
|fps_score_footprint_reference_txt_filename <br />
|Path to the reference txt file - only used when footprint reference txt is turned on. <br />
|ligand_footprint.txt<br />
|-<br />
|fps_score_foot_compare_type <br />
|Footprint similarity calculation methods (Options: Euclidean, Pearson). If Pearson, the correlation coefficient as the metric to compare the footprints. When the value is 1 then there is perfect agreement between the two footprints. WHen the value is 0 then there is poor agreement between the two footprints. If Euclidean, the Euclidean distance as the metric to compare the footprints. When the value is 0 then there is perfect agreement btween the two footprints. As the agreement gets worse between the two footprints the value increases. <br />
|Euclidean<br />
|-<br />
|fps_score_normalize_foot <br />
|normalization is used only with Euclidean distance. <br />
|no<br />
|-<br />
|fps_score_foot_comp_all_residue <br />
|If yes all residues are used for calculating the footprint. <br />
|yes<br />
|-<br />
|fps_score_choose_foot_range_type <br />
|User can use to determine the type of the range of the footprint by either specifying a residue range or defining a threshold. If specify_range, the user chooses to use a residue range and all footprints will be evaluated only on this residue range. First residue id = 1 not 0. If threshold, the user chose to use a residue range that is defined by only residues that have magnitudes that exceed the specified thresholds. (Options: specify_range, threshold) <br />
|specify_range<br />
|-<br />
|fps_score_vdw_threshold <br />
|Specify threshold for van der Waals energy, when threshold is turned on. <br />
|1<br />
|-<br />
|fps_score_es_threshold <br />
|Specify threshold for electrostatic energy, when threshold is turned on. <br />
|1<br />
|-<br />
|fps_score_hb_threshold <br />
|specify threshold for hydrogen bonds (integers). 0.5 means that all none zeros are used, when threshold is turned on. <br />
|0.5<br />
|-<br />
|fps_score_use_remainder <br />
|Interaction remainder is all remaining residues not included individually <br />
|yes<br />
|-<br />
|fps_score_rec_filename <br />
|File that contains receptor coordinates <br />
|receptor.mol2<br />
|-<br />
|fps_score_att_exp <br />
|VDW Lennard-Jones potential attractive exponent <br />
|6<br />
|-<br />
|fps_score_rep_exp <br />
|VDW Lennard-Jones potential repulsive exponent <br />
|12<br />
|-<br />
|fps_score_rep_rad_scale <br />
|Scalar multiplier of the radii for the repulsive portion of the VDW energy component ONLY <br />
|1<br />
|-<br />
|fps_score_use_distance_dependent_dielectric <br />
|Distance dependent dielectric switch <br />
|yes<br />
|-<br />
|fps_score_dielectric <br />
|Dielectric constant for electrostatic term <br />
|4.0<br />
|-<br />
|fps_score_vdw_scale <br />
|Scalar multiplier of vdw energy component <br />
|1<br />
|-<br />
|fps_score_es_scale <br />
|Scalar multiplier of es energy component <br />
|1<br />
|-<br />
|fps_score_hb_scale <br />
|Scalar multiplier of hb energy component <br />
|0<br />
|-<br />
|fps_score_internal_scale <br />
|Scalar multiplier of internal energy component <br />
|0<br />
|-<br />
|fps_score_fp_vwd_scale <br />
|Scalar multiplier of vdw footprint component <br />
|0<br />
|-<br />
|fps_score_fp_es_scale <br />
|Scalar multiplier of es footprint component <br />
|0<br />
|-<br />
|fps_score_fp_hb_scale <br />
|Scalar multiplier of hb footprint component <br />
|0<br />
|-<br />
|}<br />
<br />
===Footprint Similarity Score Output Components===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
|Footprint_similarity_score<br />
|sum of the van der Waals, electostatic, and hbond footprint similarity scores<br />
|-<br />
|FPS_vdw_energy<br />
|VDW interaction between ligand and receptor<br />
|-<br />
|FPS_es_energy<br />
|ES interaction between the ligand and receptor<br />
|-<br />
|FPS_num_hbond<br />
|number of hydrogen bonds<br />
|-<br />
|FPS_vdw+es_energy<br />
|sum of the van der Waals and electrostatic components<br />
|-<br />
|FPS_vdw_fps<br />
|vdw footprint similarity score<br />
|-<br />
|FPS_es_fps<br />
|ES footprint similarity score<br />
|-<br />
|FPS_hb_fps<br />
|hbond footprint similarity score<br />
|-<br />
|FPS_vdw_fp_numres<br />
|number of residues in the receptor considered during the calculation<br />
|-<br />
|FPS_es_fp_numres<br />
|number of residues in the receptor considered during the calculation<br />
|-<br />
|FPS_hb_fp_numres<br />
|number of residues in the receptor considered during the calculation<br />
|-<br />
|}</div>Lprentishttps://ringo.ams.stonybrook.edu/index.php?title=Scoring_Functions&diff=13092Scoring Functions2020-04-14T18:18:35Z<p>Lprentis: </p>
<hr />
<div>DOCK uses several types of scoring functions to discriminate among orientations and molecules. Scoring is requested using the score_molecules parameter. A large portion of scoring functions can be called through descriptor score (but not all). Those with descriptor score functionality will be denoted in bold. <br />
<br />
== Continuous/DOCK Cartesian Energy Score==<br />
Continuous scoring may be used to evaluate a ligand:receptor complex without the investment of a grid calculation, or to perform a more detailed calculation without the numerical approximation of the grid. '''Continuous score is implemented under Descriptor Score as well'''. Continuous score is a cartesian based score and can be combined with other Cartesian based scores with very little computational expense.<br />
<br />
===Continuous/DCE Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
|continuous_score_primary<br />
| Does the user want to perform continuous non-grid scoring as the primary scoring function?<br />
| no<br />
|-<br />
|continuous_score_secondary <br />
| Does the user want to perform continuous non-grid scoring as the secondary scoring function? <br />
|no<br />
|-<br />
|cont_score_rec_filename <br />
|File that contains receptor coordinates <br />
|receptor.mol2<br />
|-<br />
|cont_score_att_exp <br />
|VDW Lennard-Jones potential attractive exponent <br />
|6<br />
|-<br />
|cont_score_rep_exp <br />
|VDW Lennard-Jones potential repulsive exponent <br />
|12<br />
|-<br />
|cont_score_rep_rad_scale <br />
|Scalar multiplier of the radii for the repulsive portion of the vdw energy component only <br />
|1.0<br />
|-<br />
|cont_score_use_dist_dep_dielectric <br />
|Distance dependent dielectric switch <br />
|yes<br />
|-<br />
|cont_score_dielectric <br />
|Dielectric constant for the electrostatic term <br />
|<br />
|- <br />
|cont_score_vdw_scale <br />
|Scalar multiplier of vdw energy component <br />
|1 <br />
|-<br />
|cont_score_vdw_scale <br />
|Flag to turn off vdw portion of the scoring function when cont_score_vdw_scale=0 <br />
|yes<br />
|- <br />
|cont_score_es_scale <br />
|Scalar multiplier of electrostatic energy component <br />
|1.0 <br />
|-<br />
|cont_score_turn_off_es <br />
|Flag to turn off es portion of the scoring function when cont_score_es_scale = 0 <br />
|yes<br />
|-<br />
|}<br />
<br />
===Continuous/DCE Score Output Components===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
|Continuous-score<br />
|sum of the van der Waals and electrostatic interactions<br />
|-<br />
|Continuous_vdw_energy<br />
|VDW interaction between ligand and receptor<br />
|-<br />
|Continuous_es_energy<br />
|ES interaction between the ligand and receptor<br />
|-<br />
|}<br />
<br />
==Grid-Based Score== <br />
DOCK needs a fast scoring function to evaluate poses rapidly during growth. The energy grid is used for this. The grid stores the non-bonded Molecular Mechanics Potential of the receptor at each grid point. <br />
[[Image:Mm-equation.png|450px|center]]<br />
'''Grid can be called under descriptor score but it is suggested to not mix grid-based and cartesian space as that will dramatically increase computing time.'''<br />
===Grid Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
| grid_score_primary<br />
| Does the user want to perform grid-based energy scoring as the primary scoring function? || yes- <br />
|-<br />
| grid_score_rep_rad_scale<br />
| Scalar multiplier of the radii for the repulsive portion of the VDW energy component only when grid score is turned on || 1.0<br />
|-<br />
| grid_score_vdw_scale <br />
| Scalar multiplier of the VDW energy component || 1<br />
|-<br />
| grid_score_turn_off_vdw <br />
| A flag to turn off vdw portion of scoring function when grid score vdw scale = 0 || yes<br />
|-<br />
| grid_score_es_scale <br />
| Flag to scale up or down the es portion of the scoring function when es scale is turned on || 1<br />
|-<br />
| grid_score_turn_off_es <br />
| A flag to turn off es portion of scoring function when grid score es scale = 0 || yes<br />
|-<br />
| grid_score_grid_prefix <br />
| The prefix to the grid files containing the desired nrg/bmp grid || grid<br />
|-<br />
|}<br />
<br />
===Grid Score Output Components===<br />
These values will be printed in the header of the mol2 file post DOCK process.<br />
<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
| Grid_score<br />
| Sum of the VDW and ES interactions <br />
|-<br />
| Grid_vdw_energy<br />
| VDW interaction between the ligand grid<br />
|-<br />
| Grid_es_energy<br />
| ES interaction betweent eh ligand and grid<br />
|}<br />
<br />
==MultiGrid Score== <br />
The MultiGrid Score is similar to the Footprint Score described below, except that in the case of the Multi-Grid Score, the pair-wise interaction energies are computed over multiple grids rather than in Cartesian space. This is done to improve the tractability of FPS calculations as well as to make it simple to combine FPS and standard Grid Score. If the multiple grids are prepared as recommended than the sum of the interactions with each grid should equal the interaction of a standard DOCK grid representing the entire target. By default MultiGrid score will equal the sum of the interactions with all grids plus a FPS component generated by treating each grid as a protein residue. User defined scaling factors allow MultiGrid score to be set to equal Grid score, FPS score or any combination thereof. Generally, "important" receptor residues are identified before-hand based on the magnitude of their interaction with the reference ligand, then a unique grid is generated to represent each of those residues. Finally, a "remainder" grid is generated to represent all remaining receptor residues. The scoring function itself will then calculate intermolecular VDW and ES energies for the reference ligand and pose ligand on each of the grids (also called footprints), then it will calculate the footprint similarity using either the Standard Euclidean, Normalized Euclidean, or Pearson Correlation similarity metrics.<br />
<br />
'''MultiGrid can be called under descriptor score but it is suggested to not mix grid-based and cartesian space as that will dramatically increase computing time.'''<br />
<br />
===MultiGrid Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
| grid_score_primary<br />
| Does the user want to perform grid-based energy scoring as the primary scoring function? || yes- <br />
|-<br />
| grid_score_rep_rad_scale<br />
| Scalar multiplier of the radii for the repulsive portion of the VDW energy component only when grid score is turned on || 1.0<br />
|-<br />
| grid_score_vdw_scale <br />
| Scalar multiplier of the VDW energy component || 1<br />
|-<br />
| grid_score_turn_off_vdw <br />
| A flag to turn off vdw portion of scoring function when grid score vdw scale = 0 || yes<br />
|-<br />
| grid_score_es_scale <br />
| Flag to scale up or down the es portion of the scoring function when es scale is turned on || 1<br />
|-<br />
| grid_score_turn_off_es <br />
| A flag to turn off es portion of scoring function when grid score es scale = 0 || yes<br />
|-<br />
| grid_score_grid_prefix <br />
| The prefix to the grid files containing the desired nrg/bmp grid || grid<br />
|-<br />
|}<br />
<br />
===MultiGrid Score Output Components===<br />
These values will be printed in the header of the mol2 file post DOCK process.<br />
<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
| Grid_score<br />
| Sum of the VDW and ES interactions <br />
|-<br />
| Grid_vdw_energy<br />
| VDW interaction between the ligand grid<br />
|-<br />
| Grid_es_energy<br />
| ES interaction betweent eh ligand and grid<br />
|}<br />
<br />
==Footprint Similarity Score==<br />
The Footprint Similarity Score is a scoring function that calculates intermolecular hydrogen bonds and footprint comparisons, in addition to standard intermolecular energies (VDW and ES). <br />
<br />
Intermolecular Energies (VDW, ES) are calculated the same way as in Continuous Score.<br />
<br />
A geometric definition of Hydrogen bonds is employed. We define 3 atoms XD, HD, and XA as the heavy atom donor, donated hydrogen, and heavy atom acceptor, respectively. There is a hydrogen bond present if the following two conditions are met:<br />
<br />
# The distance between HD and XA is less than or equal to 2.5 angstroms;<br />
# The angle defined by XD, HD, and XA is between 120 and 180 degrees.<br />
<br />
Footprints are a per-residue decomposition of interactions between the ligand and the receptor. This can be performed for all three terms VDW, ES, HB.<br />
Two footprints can be compared in three ways: Standard Euclidean, Normalized Euclidean, Pearson Correlation.<br />
<br />
Footprints are used to gauge how similar two poses or two molecules are to one-another. For applications to virtual screening applications a reference is required.<br />
<br />
There are to choices for a reference:<br />
<br />
# One can give a mol2 file containing a reference molecule, and footprints will be calculated.<br />
# One can pass a text file containing VDW, ES, and H-bond footprints. <br />
There are different choices for selection of residues:<br />
<br />
# All residues.<br />
# Residues chosen using a threshold (union of the sets of reference and pose). The VDW, ES, and HB footprints may have different residues chosen in this case.<br />
# Selected residues.<br />
<br />
Note that for (2) and (3) the remaining residue interaction may be placed in a remainder value included in the footprint.<br />
<br />
'''Footprint Similarity Score can be called under Descriptor Score.'''<br />
<br />
===Footprint Similarity Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
|footprint_similarity_score_primary <br />
|Flag to perform footprint scoring as the primary scoring function <br />
|no<br />
|-<br />
|footprint_similarity_score_secondary <br />
|Flag to perform footprint scoring as the secondary scoring function. <br />
|no<br />
|-<br />
|fps_score_use_footprint_reference_mol2 <br />
|Use a molecule to calculate footprint reference. <br />
|no<br />
|-<br />
|fps_score_footprint_reference_mol2_filename <br />
|Path to the reference mol2 file - only used when footprint reference mol2 is turned on. <br />
|ligand_footprint.mol2<br />
|-<br />
|fps_score_use_footprint_reference_txt <br />
|Use a pre-calculated footprint reference in text format. <br />
|no<br />
|-<br />
|fps_score_footprint_reference_txt_filename <br />
|Path to the reference txt file - only used when footprint reference txt is turned on. <br />
|ligand_footprint.txt<br />
|-<br />
|fps_score_foot_compare_type <br />
|Footprint similarity calculation methods (Options: Euclidean, Pearson). If Pearson, the correlation coefficient as the metric to compare the footprints. When the value is 1 then there is perfect agreement between the two footprints. WHen the value is 0 then there is poor agreement between the two footprints. If Euclidean, the Euclidean distance as the metric to compare the footprints. When the value is 0 then there is perfect agreement btween the two footprints. As the agreement gets worse between the two footprints the value increases. <br />
|Euclidean<br />
|-<br />
|fps_score_normalize_foot <br />
|normalization is used only with Euclidean distance. <br />
|no<br />
|-<br />
|fps_score_foot_comp_all_residue <br />
|If yes all residues are used for calculating the footprint. <br />
|yes<br />
|-<br />
|fps_score_choose_foot_range_type <br />
|User can use to determine the type of the range of the footprint by either specifying a residue range or defining a threshold. If specify_range, the user chooses to use a residue range and all footprints will be evaluated only on this residue range. First residue id = 1 not 0. If threshold, the user chose to use a residue range that is defined by only residues that have magnitudes that exceed the specified thresholds. (Options: specify_range, threshold) <br />
|specify_range<br />
|-<br />
|fps_score_vdw_threshold <br />
|Specify threshold for van der Waals energy, when threshold is turned on. <br />
|1<br />
|-<br />
|fps_score_es_threshold <br />
|Specify threshold for electrostatic energy, when threshold is turned on. <br />
|1<br />
|-<br />
|fps_score_hb_threshold <br />
|specify threshold for hydrogen bonds (integers). 0.5 means that all none zeros are used, when threshold is turned on. <br />
|0.5<br />
|-<br />
|fps_score_use_remainder <br />
|Interaction remainder is all remaining residues not included individually <br />
|yes<br />
|-<br />
|fps_score_rec_filename <br />
|File that contains receptor coordinates <br />
|receptor.mol2<br />
|-<br />
|fps_score_att_exp <br />
|VDW Lennard-Jones potential attractive exponent <br />
|6<br />
|-<br />
|fps_score_rep_exp <br />
|VDW Lennard-Jones potential repulsive exponent <br />
|12<br />
|-<br />
|fps_score_rep_rad_scale <br />
|Scalar multiplier of the radii for the repulsive portion of the VDW energy component ONLY <br />
|1<br />
|-<br />
|fps_score_use_distance_dependent_dielectric <br />
|Distance dependent dielectric switch <br />
|yes<br />
|-<br />
|fps_score_dielectric <br />
|Dielectric constant for electrostatic term <br />
|4.0<br />
|-<br />
|fps_score_vdw_scale <br />
|Scalar multiplier of vdw energy component <br />
|1<br />
|-<br />
|fps_score_es_scale <br />
|Scalar multiplier of es energy component <br />
|1<br />
|-<br />
|fps_score_hb_scale <br />
|Scalar multiplier of hb energy component <br />
|0<br />
|-<br />
|fps_score_internal_scale <br />
|Scalar multiplier of internal energy component <br />
|0<br />
|-<br />
|fps_score_fp_vwd_scale <br />
|Scalar multiplier of vdw footprint component <br />
|0<br />
|-<br />
|fps_score_fp_es_scale <br />
|Scalar multiplier of es footprint component <br />
|0<br />
|-<br />
|fps_score_fp_hb_scale <br />
|Scalar multiplier of hb footprint component <br />
|0<br />
|-<br />
|}<br />
<br />
===Footprint Similarity Score Output Components===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
|Footprint_similarity_score<br />
|sum of the van der Waals, electostatic, and hbond footprint similarity scores<br />
|-<br />
|FPS_vdw_energy<br />
|VDW interaction between ligand and receptor<br />
|-<br />
|FPS_es_energy<br />
|ES interaction between the ligand and receptor<br />
|-<br />
|FPS_num_hbond<br />
|number of hydrogen bonds<br />
|-<br />
|FPS_vdw+es_energy<br />
|sum of the van der Waals and electrostatic components<br />
|-<br />
|FPS_vdw_fps<br />
|vdw footprint similarity score<br />
|-<br />
|FPS_es_fps<br />
|ES footprint similarity score<br />
|-<br />
|FPS_hb_fps<br />
|hbond footprint similarity score<br />
|-<br />
|FPS_vdw_fp_numres<br />
|number of residues in the receptor considered during the calculation<br />
|-<br />
|FPS_es_fp_numres<br />
|number of residues in the receptor considered during the calculation<br />
|-<br />
|FPS_hb_fp_numres<br />
|number of residues in the receptor considered during the calculation<br />
|-<br />
|}</div>Lprentishttps://ringo.ams.stonybrook.edu/index.php?title=Scoring_Functions&diff=13091Scoring Functions2020-04-14T18:16:13Z<p>Lprentis: </p>
<hr />
<div>DOCK uses several types of scoring functions to discriminate among orientations and molecules. Scoring is requested using the score_molecules parameter. A large portion of scoring functions can be called through descriptor score (but not all). Those with descriptor score functionality will be denoted in bold. <br />
<br />
== Continuous/DOCK Cartesian Energy Score==<br />
Continuous scoring may be used to evaluate a ligand:receptor complex without the investment of a grid calculation, or to perform a more detailed calculation without the numerical approximation of the grid. '''Continuous score is implemented under Descriptor Score as well'''. Continuous score is a cartesian based score and can be combined with other Cartesian based scores with very little computational expense.<br />
<br />
===Continuous/DCE Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
|continuous_score_primary<br />
| Does the user want to perform continuous non-grid scoring as the primary scoring function?<br />
| no<br />
|-<br />
|continuous_score_secondary <br />
| Does the user want to perform continuous non-grid scoring as the secondary scoring function? <br />
|no<br />
|-<br />
|cont_score_rec_filename <br />
|File that contains receptor coordinates <br />
|receptor.mol2<br />
|-<br />
|cont_score_att_exp <br />
|VDW Lennard-Jones potential attractive exponent <br />
|6<br />
|-<br />
|cont_score_rep_exp <br />
|VDW Lennard-Jones potential repulsive exponent <br />
|12<br />
|-<br />
|cont_score_rep_rad_scale <br />
|Scalar multiplier of the radii for the repulsive portion of the vdw energy component only <br />
|1.0<br />
|-<br />
|cont_score_use_dist_dep_dielectric <br />
|Distance dependent dielectric switch <br />
|yes<br />
|-<br />
|cont_score_dielectric <br />
|Dielectric constant for the electrostatic term <br />
|<br />
|- <br />
|cont_score_vdw_scale <br />
|Scalar multiplier of vdw energy component <br />
|1 <br />
|-<br />
|cont_score_vdw_scale <br />
|Flag to turn off vdw portion of the scoring function when cont_score_vdw_scale=0 <br />
|yes<br />
|- <br />
|cont_score_es_scale <br />
|Scalar multiplier of electrostatic energy component <br />
|1.0 <br />
|-<br />
|cont_score_turn_off_es <br />
|Flag to turn off es portion of the scoring function when cont_score_es_scale = 0 <br />
|yes<br />
|-<br />
|}<br />
<br />
===Continuous/DCE Score Output Components===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
|Continuous-score<br />
|sum of the van der Waals and electrostatic interactions<br />
|-<br />
|Continuous_vdw_energy<br />
|VDW interaction between ligand and receptor<br />
|-<br />
|Continuous_es_energy<br />
|ES interaction between the ligand and receptor<br />
|-<br />
|}<br />
<br />
==Grid-Based Score== <br />
DOCK needs a fast scoring function to evaluate poses rapidly during growth. The energy grid is used for this. The grid stores the non-bonded Molecular Mechanics Potential of the receptor at each grid point. <br />
[[Image:Mm-equation.png|450px|center]]<br />
'''Grid can be called under descriptor score but it is suggested to not mix grid-based and cartesian space as that will dramatically increase computing time.'''<br />
===Grid Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
| grid_score_primary<br />
| Does the user want to perform grid-based energy scoring as the primary scoring function? || yes- <br />
|-<br />
| grid_score_rep_rad_scale<br />
| Scalar multiplier of the radii for the repulsive portion of the VDW energy component only when grid score is turned on || 1.0<br />
|-<br />
| grid_score_vdw_scale <br />
| Scalar multiplier of the VDW energy component || 1<br />
|-<br />
| grid_score_turn_off_vdw <br />
| A flag to turn off vdw portion of scoring function when grid score vdw scale = 0 || yes<br />
|-<br />
| grid_score_es_scale <br />
| Flag to scale up or down the es portion of the scoring function when es scale is turned on || 1<br />
|-<br />
| grid_score_turn_off_es <br />
| A flag to turn off es portion of scoring function when grid score es scale = 0 || yes<br />
|-<br />
| grid_score_grid_prefix <br />
| The prefix to the grid files containing the desired nrg/bmp grid || grid<br />
|-<br />
|}<br />
<br />
===Grid Score Output Components===<br />
These values will be printed in the header of the mol2 file post DOCK process.<br />
<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
| Grid_score<br />
| Sum of the VDW and ES interactions <br />
|-<br />
| Grid_vdw_energy<br />
| VDW interaction between the ligand grid<br />
|-<br />
| Grid_es_energy<br />
| ES interaction betweent eh ligand and grid<br />
|}<br />
<br />
<br />
==Footprint Similarity Score==<br />
The Footprint Similarity Score is a scoring function that calculates intermolecular hydrogen bonds and footprint comparisons, in addition to standard intermolecular energies (VDW and ES). <br />
<br />
Intermolecular Energies (VDW, ES) are calculated the same way as in Continuous Score.<br />
<br />
A geometric definition of Hydrogen bonds is employed. We define 3 atoms XD, HD, and XA as the heavy atom donor, donated hydrogen, and heavy atom acceptor, respectively. There is a hydrogen bond present if the following two conditions are met:<br />
<br />
# The distance between HD and XA is less than or equal to 2.5 angstroms;<br />
# The angle defined by XD, HD, and XA is between 120 and 180 degrees.<br />
<br />
Footprints are a per-residue decomposition of interactions between the ligand and the receptor. This can be performed for all three terms VDW, ES, HB.<br />
Two footprints can be compared in three ways: Standard Euclidean, Normalized Euclidean, Pearson Correlation.<br />
<br />
Footprints are used to gauge how similar two poses or two molecules are to one-another. For applications to virtual screening applications a reference is required.<br />
<br />
There are to choices for a reference:<br />
<br />
# One can give a mol2 file containing a reference molecule, and footprints will be calculated.<br />
# One can pass a text file containing VDW, ES, and H-bond footprints. <br />
There are different choices for selection of residues:<br />
<br />
# All residues.<br />
# Residues chosen using a threshold (union of the sets of reference and pose). The VDW, ES, and HB footprints may have different residues chosen in this case.<br />
# Selected residues.<br />
<br />
Note that for (2) and (3) the remaining residue interaction may be placed in a remainder value included in the footprint.<br />
<br />
'''Footprint Similarity Score can be called under Descriptor Score.'''<br />
<br />
===Footprint Similarity Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
|footprint_similarity_score_primary <br />
|Flag to perform footprint scoring as the primary scoring function <br />
|no<br />
|-<br />
|footprint_similarity_score_secondary <br />
|Flag to perform footprint scoring as the secondary scoring function. <br />
|no<br />
|-<br />
|fps_score_use_footprint_reference_mol2 <br />
|Use a molecule to calculate footprint reference. <br />
|no<br />
|-<br />
|fps_score_footprint_reference_mol2_filename <br />
|Path to the reference mol2 file - only used when footprint reference mol2 is turned on. <br />
|ligand_footprint.mol2<br />
|-<br />
|fps_score_use_footprint_reference_txt <br />
|Use a pre-calculated footprint reference in text format. <br />
|no<br />
|-<br />
|fps_score_footprint_reference_txt_filename <br />
|Path to the reference txt file - only used when footprint reference txt is turned on. <br />
|ligand_footprint.txt<br />
|-<br />
|fps_score_foot_compare_type <br />
|Footprint similarity calculation methods (Options: Euclidean, Pearson). If Pearson, the correlation coefficient as the metric to compare the footprints. When the value is 1 then there is perfect agreement between the two footprints. WHen the value is 0 then there is poor agreement between the two footprints. If Euclidean, the Euclidean distance as the metric to compare the footprints. When the value is 0 then there is perfect agreement btween the two footprints. As the agreement gets worse between the two footprints the value increases. <br />
|Euclidean<br />
|-<br />
|fps_score_normalize_foot <br />
|normalization is used only with Euclidean distance. <br />
|no<br />
|-<br />
|fps_score_foot_comp_all_residue <br />
|If yes all residues are used for calculating the footprint. <br />
|yes<br />
|-<br />
|fps_score_choose_foot_range_type <br />
|User can use to determine the type of the range of the footprint by either specifying a residue range or defining a threshold. If specify_range, the user chooses to use a residue range and all footprints will be evaluated only on this residue range. First residue id = 1 not 0. If threshold, the user chose to use a residue range that is defined by only residues that have magnitudes that exceed the specified thresholds. (Options: specify_range, threshold) <br />
|specify_range<br />
|-<br />
|fps_score_vdw_threshold <br />
|Specify threshold for van der Waals energy, when threshold is turned on. <br />
|1<br />
|-<br />
|fps_score_es_threshold <br />
|Specify threshold for electrostatic energy, when threshold is turned on. <br />
|1<br />
|-<br />
|fps_score_hb_threshold <br />
|specify threshold for hydrogen bonds (integers). 0.5 means that all none zeros are used, when threshold is turned on. <br />
|0.5<br />
|-<br />
|fps_score_use_remainder <br />
|Interaction remainder is all remaining residues not included individually <br />
|yes<br />
|-<br />
|fps_score_rec_filename <br />
|File that contains receptor coordinates <br />
|receptor.mol2<br />
|-<br />
|fps_score_att_exp <br />
|VDW Lennard-Jones potential attractive exponent <br />
|6<br />
|-<br />
|fps_score_rep_exp <br />
|VDW Lennard-Jones potential repulsive exponent <br />
|12<br />
|-<br />
|fps_score_rep_rad_scale <br />
|Scalar multiplier of the radii for the repulsive portion of the VDW energy component ONLY <br />
|1<br />
|-<br />
|fps_score_use_distance_dependent_dielectric <br />
|Distance dependent dielectric switch <br />
|yes<br />
|-<br />
|fps_score_dielectric <br />
|Dielectric constant for electrostatic term <br />
|4.0<br />
|-<br />
|fps_score_vdw_scale <br />
|Scalar multiplier of vdw energy component <br />
|1<br />
|-<br />
|fps_score_es_scale <br />
|Scalar multiplier of es energy component <br />
|1<br />
|-<br />
|fps_score_hb_scale <br />
|Scalar multiplier of hb energy component <br />
|0<br />
|-<br />
|fps_score_internal_scale <br />
|Scalar multiplier of internal energy component <br />
|0<br />
|-<br />
|fps_score_fp_vwd_scale <br />
|Scalar multiplier of vdw footprint component <br />
|0<br />
|-<br />
|fps_score_fp_es_scale <br />
|Scalar multiplier of es footprint component <br />
|0<br />
|-<br />
|fps_score_fp_hb_scale <br />
|Scalar multiplier of hb footprint component <br />
|0<br />
|-<br />
|}<br />
<br />
===Footprint Similarity Score Output Components===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
|Footprint_similarity_score<br />
|sum of the van der Waals, electostatic, and hbond footprint similarity scores<br />
|-<br />
|FPS_vdw_energy<br />
|VDW interaction between ligand and receptor<br />
|-<br />
|FPS_es_energy<br />
|ES interaction between the ligand and receptor<br />
|-<br />
|FPS_num_hbond<br />
|number of hydrogen bonds<br />
|-<br />
|FPS_vdw+es_energy<br />
|sum of the van der Waals and electrostatic components<br />
|-<br />
|FPS_vdw_fps<br />
|vdw footprint similarity score<br />
|-<br />
|FPS_es_fps<br />
|ES footprint similarity score<br />
|-<br />
|FPS_hb_fps<br />
|hbond footprint similarity score<br />
|-<br />
|FPS_vdw_fp_numres<br />
|number of residues in the receptor considered during the calculation<br />
|-<br />
|FPS_es_fp_numres<br />
|number of residues in the receptor considered during the calculation<br />
|-<br />
|FPS_hb_fp_numres<br />
|number of residues in the receptor considered during the calculation<br />
|-<br />
|}</div>Lprentishttps://ringo.ams.stonybrook.edu/index.php?title=Scoring_Functions&diff=13090Scoring Functions2020-04-14T18:15:51Z<p>Lprentis: </p>
<hr />
<div>DOCK uses several types of scoring functions to discriminate among orientations and molecules. Scoring is requested using the score_molecules parameter. A large portion of scoring functions can be called through descriptor score (but not all). Those with descriptor score functionality will be denoted as such. <br />
<br />
== Continuous/DOCK Cartesian Energy Score==<br />
Continuous scoring may be used to evaluate a ligand:receptor complex without the investment of a grid calculation, or to perform a more detailed calculation without the numerical approximation of the grid. '''Continuous score is implemented under Descriptor Score as well'''. Continuous score is a cartesian based score and can be combined with other Cartesian based scores with very little computational expense.<br />
<br />
===Continuous/DCE Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
|continuous_score_primary<br />
| Does the user want to perform continuous non-grid scoring as the primary scoring function?<br />
| no<br />
|-<br />
|continuous_score_secondary <br />
| Does the user want to perform continuous non-grid scoring as the secondary scoring function? <br />
|no<br />
|-<br />
|cont_score_rec_filename <br />
|File that contains receptor coordinates <br />
|receptor.mol2<br />
|-<br />
|cont_score_att_exp <br />
|VDW Lennard-Jones potential attractive exponent <br />
|6<br />
|-<br />
|cont_score_rep_exp <br />
|VDW Lennard-Jones potential repulsive exponent <br />
|12<br />
|-<br />
|cont_score_rep_rad_scale <br />
|Scalar multiplier of the radii for the repulsive portion of the vdw energy component only <br />
|1.0<br />
|-<br />
|cont_score_use_dist_dep_dielectric <br />
|Distance dependent dielectric switch <br />
|yes<br />
|-<br />
|cont_score_dielectric <br />
|Dielectric constant for the electrostatic term <br />
|<br />
|- <br />
|cont_score_vdw_scale <br />
|Scalar multiplier of vdw energy component <br />
|1 <br />
|-<br />
|cont_score_vdw_scale <br />
|Flag to turn off vdw portion of the scoring function when cont_score_vdw_scale=0 <br />
|yes<br />
|- <br />
|cont_score_es_scale <br />
|Scalar multiplier of electrostatic energy component <br />
|1.0 <br />
|-<br />
|cont_score_turn_off_es <br />
|Flag to turn off es portion of the scoring function when cont_score_es_scale = 0 <br />
|yes<br />
|-<br />
|}<br />
<br />
===Continuous/DCE Score Output Components===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
|Continuous-score<br />
|sum of the van der Waals and electrostatic interactions<br />
|-<br />
|Continuous_vdw_energy<br />
|VDW interaction between ligand and receptor<br />
|-<br />
|Continuous_es_energy<br />
|ES interaction between the ligand and receptor<br />
|-<br />
|}<br />
<br />
==Grid-Based Score== <br />
DOCK needs a fast scoring function to evaluate poses rapidly during growth. The energy grid is used for this. The grid stores the non-bonded Molecular Mechanics Potential of the receptor at each grid point. <br />
[[Image:Mm-equation.png|450px|center]]<br />
'''Grid can be called under descriptor score but it is suggested to not mix grid-based and cartesian space as that will dramatically increase computing time.'''<br />
===Grid Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
| grid_score_primary<br />
| Does the user want to perform grid-based energy scoring as the primary scoring function? || yes- <br />
|-<br />
| grid_score_rep_rad_scale<br />
| Scalar multiplier of the radii for the repulsive portion of the VDW energy component only when grid score is turned on || 1.0<br />
|-<br />
| grid_score_vdw_scale <br />
| Scalar multiplier of the VDW energy component || 1<br />
|-<br />
| grid_score_turn_off_vdw <br />
| A flag to turn off vdw portion of scoring function when grid score vdw scale = 0 || yes<br />
|-<br />
| grid_score_es_scale <br />
| Flag to scale up or down the es portion of the scoring function when es scale is turned on || 1<br />
|-<br />
| grid_score_turn_off_es <br />
| A flag to turn off es portion of scoring function when grid score es scale = 0 || yes<br />
|-<br />
| grid_score_grid_prefix <br />
| The prefix to the grid files containing the desired nrg/bmp grid || grid<br />
|-<br />
|}<br />
<br />
===Grid Score Output Components===<br />
These values will be printed in the header of the mol2 file post DOCK process.<br />
<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
| Grid_score<br />
| Sum of the VDW and ES interactions <br />
|-<br />
| Grid_vdw_energy<br />
| VDW interaction between the ligand grid<br />
|-<br />
| Grid_es_energy<br />
| ES interaction betweent eh ligand and grid<br />
|}<br />
<br />
<br />
==Footprint Similarity Score==<br />
The Footprint Similarity Score is a scoring function that calculates intermolecular hydrogen bonds and footprint comparisons, in addition to standard intermolecular energies (VDW and ES). <br />
<br />
Intermolecular Energies (VDW, ES) are calculated the same way as in Continuous Score.<br />
<br />
A geometric definition of Hydrogen bonds is employed. We define 3 atoms XD, HD, and XA as the heavy atom donor, donated hydrogen, and heavy atom acceptor, respectively. There is a hydrogen bond present if the following two conditions are met:<br />
<br />
# The distance between HD and XA is less than or equal to 2.5 angstroms;<br />
# The angle defined by XD, HD, and XA is between 120 and 180 degrees.<br />
<br />
Footprints are a per-residue decomposition of interactions between the ligand and the receptor. This can be performed for all three terms VDW, ES, HB.<br />
Two footprints can be compared in three ways: Standard Euclidean, Normalized Euclidean, Pearson Correlation.<br />
<br />
Footprints are used to gauge how similar two poses or two molecules are to one-another. For applications to virtual screening applications a reference is required.<br />
<br />
There are to choices for a reference:<br />
<br />
# One can give a mol2 file containing a reference molecule, and footprints will be calculated.<br />
# One can pass a text file containing VDW, ES, and H-bond footprints. <br />
There are different choices for selection of residues:<br />
<br />
# All residues.<br />
# Residues chosen using a threshold (union of the sets of reference and pose). The VDW, ES, and HB footprints may have different residues chosen in this case.<br />
# Selected residues.<br />
<br />
Note that for (2) and (3) the remaining residue interaction may be placed in a remainder value included in the footprint.<br />
<br />
'''Footprint Similarity Score can be called under Descriptor Score.'''<br />
<br />
===Footprint Similarity Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
|footprint_similarity_score_primary <br />
|Flag to perform footprint scoring as the primary scoring function <br />
|no<br />
|-<br />
|footprint_similarity_score_secondary <br />
|Flag to perform footprint scoring as the secondary scoring function. <br />
|no<br />
|-<br />
|fps_score_use_footprint_reference_mol2 <br />
|Use a molecule to calculate footprint reference. <br />
|no<br />
|-<br />
|fps_score_footprint_reference_mol2_filename <br />
|Path to the reference mol2 file - only used when footprint reference mol2 is turned on. <br />
|ligand_footprint.mol2<br />
|-<br />
|fps_score_use_footprint_reference_txt <br />
|Use a pre-calculated footprint reference in text format. <br />
|no<br />
|-<br />
|fps_score_footprint_reference_txt_filename <br />
|Path to the reference txt file - only used when footprint reference txt is turned on. <br />
|ligand_footprint.txt<br />
|-<br />
|fps_score_foot_compare_type <br />
|Footprint similarity calculation methods (Options: Euclidean, Pearson). If Pearson, the correlation coefficient as the metric to compare the footprints. When the value is 1 then there is perfect agreement between the two footprints. WHen the value is 0 then there is poor agreement between the two footprints. If Euclidean, the Euclidean distance as the metric to compare the footprints. When the value is 0 then there is perfect agreement btween the two footprints. As the agreement gets worse between the two footprints the value increases. <br />
|Euclidean<br />
|-<br />
|fps_score_normalize_foot <br />
|normalization is used only with Euclidean distance. <br />
|no<br />
|-<br />
|fps_score_foot_comp_all_residue <br />
|If yes all residues are used for calculating the footprint. <br />
|yes<br />
|-<br />
|fps_score_choose_foot_range_type <br />
|User can use to determine the type of the range of the footprint by either specifying a residue range or defining a threshold. If specify_range, the user chooses to use a residue range and all footprints will be evaluated only on this residue range. First residue id = 1 not 0. If threshold, the user chose to use a residue range that is defined by only residues that have magnitudes that exceed the specified thresholds. (Options: specify_range, threshold) <br />
|specify_range<br />
|-<br />
|fps_score_vdw_threshold <br />
|Specify threshold for van der Waals energy, when threshold is turned on. <br />
|1<br />
|-<br />
|fps_score_es_threshold <br />
|Specify threshold for electrostatic energy, when threshold is turned on. <br />
|1<br />
|-<br />
|fps_score_hb_threshold <br />
|specify threshold for hydrogen bonds (integers). 0.5 means that all none zeros are used, when threshold is turned on. <br />
|0.5<br />
|-<br />
|fps_score_use_remainder <br />
|Interaction remainder is all remaining residues not included individually <br />
|yes<br />
|-<br />
|fps_score_rec_filename <br />
|File that contains receptor coordinates <br />
|receptor.mol2<br />
|-<br />
|fps_score_att_exp <br />
|VDW Lennard-Jones potential attractive exponent <br />
|6<br />
|-<br />
|fps_score_rep_exp <br />
|VDW Lennard-Jones potential repulsive exponent <br />
|12<br />
|-<br />
|fps_score_rep_rad_scale <br />
|Scalar multiplier of the radii for the repulsive portion of the VDW energy component ONLY <br />
|1<br />
|-<br />
|fps_score_use_distance_dependent_dielectric <br />
|Distance dependent dielectric switch <br />
|yes<br />
|-<br />
|fps_score_dielectric <br />
|Dielectric constant for electrostatic term <br />
|4.0<br />
|-<br />
|fps_score_vdw_scale <br />
|Scalar multiplier of vdw energy component <br />
|1<br />
|-<br />
|fps_score_es_scale <br />
|Scalar multiplier of es energy component <br />
|1<br />
|-<br />
|fps_score_hb_scale <br />
|Scalar multiplier of hb energy component <br />
|0<br />
|-<br />
|fps_score_internal_scale <br />
|Scalar multiplier of internal energy component <br />
|0<br />
|-<br />
|fps_score_fp_vwd_scale <br />
|Scalar multiplier of vdw footprint component <br />
|0<br />
|-<br />
|fps_score_fp_es_scale <br />
|Scalar multiplier of es footprint component <br />
|0<br />
|-<br />
|fps_score_fp_hb_scale <br />
|Scalar multiplier of hb footprint component <br />
|0<br />
|-<br />
|}<br />
<br />
===Footprint Similarity Score Output Components===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
|Footprint_similarity_score<br />
|sum of the van der Waals, electostatic, and hbond footprint similarity scores<br />
|-<br />
|FPS_vdw_energy<br />
|VDW interaction between ligand and receptor<br />
|-<br />
|FPS_es_energy<br />
|ES interaction between the ligand and receptor<br />
|-<br />
|FPS_num_hbond<br />
|number of hydrogen bonds<br />
|-<br />
|FPS_vdw+es_energy<br />
|sum of the van der Waals and electrostatic components<br />
|-<br />
|FPS_vdw_fps<br />
|vdw footprint similarity score<br />
|-<br />
|FPS_es_fps<br />
|ES footprint similarity score<br />
|-<br />
|FPS_hb_fps<br />
|hbond footprint similarity score<br />
|-<br />
|FPS_vdw_fp_numres<br />
|number of residues in the receptor considered during the calculation<br />
|-<br />
|FPS_es_fp_numres<br />
|number of residues in the receptor considered during the calculation<br />
|-<br />
|FPS_hb_fp_numres<br />
|number of residues in the receptor considered during the calculation<br />
|-<br />
|}</div>Lprentishttps://ringo.ams.stonybrook.edu/index.php?title=DOCK_Abbreviations_Guide&diff=13089DOCK Abbreviations Guide2020-04-14T18:14:48Z<p>Lprentis: </p>
<hr />
<div>This is a DOCK abbreviations guide for the language used in the user manual and online tutorials.<br />
<br />
* AG = Anchor and Grow<br />
* CD = Covalent De Novo<br />
* CV = Covalent Attach and Grow<br />
* DN = De Novo<br />
* GA = Genetic Algorithm<br />
* ES = Electrostatic <br />
* VDW = Van der Waals<br />
* DCE = DOCK Cartesian Energy/Continuous Score<br />
* FMS = Pharmacophore Matching Similarity<br />
* FPS = Footprint Matching Similarity<br />
* HMS = Hungarian Matching Similarity<br />
* MGE = Multigrid Energy Score<br />
* MGS = Multigrid Score (MGE +FPS)<br />
* VOS = Volume Overlap Similarity</div>Lprentishttps://ringo.ams.stonybrook.edu/index.php?title=Scoring_Functions&diff=13088Scoring Functions2020-04-14T18:13:10Z<p>Lprentis: /* Footprint Similarity Score Output Components */</p>
<hr />
<div>DOCK uses several types of scoring functions to discriminate among orientations and molecules. Scoring is requested using the score_molecules parameter. A large portion of scoring functions can be called through descriptor score (but not all). Those with descriptor score functionality will be denoted as such. <br />
<br />
==Grid-Based Score== <br />
DOCK needs a fast scoring function to evaluate poses rapidly during growth. The energy grid is used for this. The grid stores the non-bonded Molecular Mechanics Potential of the receptor at each grid point. <br />
[[Image:Mm-equation.png|450px|center]]<br />
'''Grid can be called under descriptor score but it is suggested to not mix grid-based and cartesian space as that will dramatically increase computing time.'''<br />
===Grid Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
| grid_score_primary<br />
| Does the user want to perform grid-based energy scoring as the primary scoring function? || yes- <br />
|-<br />
| grid_score_rep_rad_scale<br />
| Scalar multiplier of the radii for the repulsive portion of the VDW energy component only when grid score is turned on || 1.0<br />
|-<br />
| grid_score_vdw_scale <br />
| Scalar multiplier of the VDW energy component || 1<br />
|-<br />
| grid_score_turn_off_vdw <br />
| A flag to turn off vdw portion of scoring function when grid score vdw scale = 0 || yes<br />
|-<br />
| grid_score_es_scale <br />
| Flag to scale up or down the es portion of the scoring function when es scale is turned on || 1<br />
|-<br />
| grid_score_turn_off_es <br />
| A flag to turn off es portion of scoring function when grid score es scale = 0 || yes<br />
|-<br />
| grid_score_grid_prefix <br />
| The prefix to the grid files containing the desired nrg/bmp grid || grid<br />
|-<br />
|}<br />
<br />
===Grid Score Output Components===<br />
These values will be printed in the header of the mol2 file post DOCK process.<br />
<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
| Grid_score<br />
| Sum of the VDW and ES interactions <br />
|-<br />
| Grid_vdw_energy<br />
| VDW interaction between the ligand grid<br />
|-<br />
| Grid_es_energy<br />
| ES interaction betweent eh ligand and grid<br />
|}<br />
<br />
== Continuous/DOCK Cartesian Energy Score==<br />
Continuous scoring may be used to evaluate a ligand:receptor complex without the investment of a grid calculation, or to perform a more detailed calculation without the numerical approximation of the grid. '''Continuous score is implemented under Descriptor Score as well'''. Continuous score is a cartesian based score and can be combined with other Cartesian based scores with very little computational expense.<br />
<br />
===Continuous/DCE Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
|continuous_score_primary<br />
| Does the user want to perform continuous non-grid scoring as the primary scoring function?<br />
| no<br />
|-<br />
|continuous_score_secondary <br />
| Does the user want to perform continuous non-grid scoring as the secondary scoring function? <br />
|no<br />
|-<br />
|cont_score_rec_filename <br />
|File that contains receptor coordinates <br />
|receptor.mol2<br />
|-<br />
|cont_score_att_exp <br />
|VDW Lennard-Jones potential attractive exponent <br />
|6<br />
|-<br />
|cont_score_rep_exp <br />
|VDW Lennard-Jones potential repulsive exponent <br />
|12<br />
|-<br />
|cont_score_rep_rad_scale <br />
|Scalar multiplier of the radii for the repulsive portion of the vdw energy component only <br />
|1.0<br />
|-<br />
|cont_score_use_dist_dep_dielectric <br />
|Distance dependent dielectric switch <br />
|yes<br />
|-<br />
|cont_score_dielectric <br />
|Dielectric constant for the electrostatic term <br />
|<br />
|- <br />
|cont_score_vdw_scale <br />
|Scalar multiplier of vdw energy component <br />
|1 <br />
|-<br />
|cont_score_vdw_scale <br />
|Flag to turn off vdw portion of the scoring function when cont_score_vdw_scale=0 <br />
|yes<br />
|- <br />
|cont_score_es_scale <br />
|Scalar multiplier of electrostatic energy component <br />
|1.0 <br />
|-<br />
|cont_score_turn_off_es <br />
|Flag to turn off es portion of the scoring function when cont_score_es_scale = 0 <br />
|yes<br />
|-<br />
|}<br />
<br />
===Continuous/DCE Score Output Components===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
|Continuous-score<br />
|sum of the van der Waals and electrostatic interactions<br />
|-<br />
|Continuous_vdw_energy<br />
|VDW interaction between ligand and receptor<br />
|-<br />
|Continuous_es_energy<br />
|ES interaction between the ligand and receptor<br />
|-<br />
|}<br />
<br />
==Footprint Similarity Score==<br />
The Footprint Similarity Score is a scoring function that calculates intermolecular hydrogen bonds and footprint comparisons, in addition to standard intermolecular energies (VDW and ES). <br />
<br />
Intermolecular Energies (VDW, ES) are calculated the same way as in Continuous Score.<br />
<br />
A geometric definition of Hydrogen bonds is employed. We define 3 atoms XD, HD, and XA as the heavy atom donor, donated hydrogen, and heavy atom acceptor, respectively. There is a hydrogen bond present if the following two conditions are met:<br />
<br />
# The distance between HD and XA is less than or equal to 2.5 angstroms;<br />
# The angle defined by XD, HD, and XA is between 120 and 180 degrees.<br />
<br />
Footprints are a per-residue decomposition of interactions between the ligand and the receptor. This can be performed for all three terms VDW, ES, HB.<br />
Two footprints can be compared in three ways: Standard Euclidean, Normalized Euclidean, Pearson Correlation.<br />
<br />
Footprints are used to gauge how similar two poses or two molecules are to one-another. For applications to virtual screening applications a reference is required.<br />
<br />
There are to choices for a reference:<br />
<br />
# One can give a mol2 file containing a reference molecule, and footprints will be calculated.<br />
# One can pass a text file containing VDW, ES, and H-bond footprints. <br />
There are different choices for selection of residues:<br />
<br />
# All residues.<br />
# Residues chosen using a threshold (union of the sets of reference and pose). The VDW, ES, and HB footprints may have different residues chosen in this case.<br />
# Selected residues.<br />
<br />
Note that for (2) and (3) the remaining residue interaction may be placed in a remainder value included in the footprint.<br />
<br />
'''Footprint Similarity Score can be called under Descriptor Score.'''<br />
<br />
===Footprint Similarity Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
|footprint_similarity_score_primary <br />
|Flag to perform footprint scoring as the primary scoring function <br />
|no<br />
|-<br />
|footprint_similarity_score_secondary <br />
|Flag to perform footprint scoring as the secondary scoring function. <br />
|no<br />
|-<br />
|fps_score_use_footprint_reference_mol2 <br />
|Use a molecule to calculate footprint reference. <br />
|no<br />
|-<br />
|fps_score_footprint_reference_mol2_filename <br />
|Path to the reference mol2 file - only used when footprint reference mol2 is turned on. <br />
|ligand_footprint.mol2<br />
|-<br />
|fps_score_use_footprint_reference_txt <br />
|Use a pre-calculated footprint reference in text format. <br />
|no<br />
|-<br />
|fps_score_footprint_reference_txt_filename <br />
|Path to the reference txt file - only used when footprint reference txt is turned on. <br />
|ligand_footprint.txt<br />
|-<br />
|fps_score_foot_compare_type <br />
|Footprint similarity calculation methods (Options: Euclidean, Pearson). If Pearson, the correlation coefficient as the metric to compare the footprints. When the value is 1 then there is perfect agreement between the two footprints. WHen the value is 0 then there is poor agreement between the two footprints. If Euclidean, the Euclidean distance as the metric to compare the footprints. When the value is 0 then there is perfect agreement btween the two footprints. As the agreement gets worse between the two footprints the value increases. <br />
|Euclidean<br />
|-<br />
|fps_score_normalize_foot <br />
|normalization is used only with Euclidean distance. <br />
|no<br />
|-<br />
|fps_score_foot_comp_all_residue <br />
|If yes all residues are used for calculating the footprint. <br />
|yes<br />
|-<br />
|fps_score_choose_foot_range_type <br />
|User can use to determine the type of the range of the footprint by either specifying a residue range or defining a threshold. If specify_range, the user chooses to use a residue range and all footprints will be evaluated only on this residue range. First residue id = 1 not 0. If threshold, the user chose to use a residue range that is defined by only residues that have magnitudes that exceed the specified thresholds. (Options: specify_range, threshold) <br />
|specify_range<br />
|-<br />
|fps_score_vdw_threshold <br />
|Specify threshold for van der Waals energy, when threshold is turned on. <br />
|1<br />
|-<br />
|fps_score_es_threshold <br />
|Specify threshold for electrostatic energy, when threshold is turned on. <br />
|1<br />
|-<br />
|fps_score_hb_threshold <br />
|specify threshold for hydrogen bonds (integers). 0.5 means that all none zeros are used, when threshold is turned on. <br />
|0.5<br />
|-<br />
|fps_score_use_remainder <br />
|Interaction remainder is all remaining residues not included individually <br />
|yes<br />
|-<br />
|fps_score_rec_filename <br />
|File that contains receptor coordinates <br />
|receptor.mol2<br />
|-<br />
|fps_score_att_exp <br />
|VDW Lennard-Jones potential attractive exponent <br />
|6<br />
|-<br />
|fps_score_rep_exp <br />
|VDW Lennard-Jones potential repulsive exponent <br />
|12<br />
|-<br />
|fps_score_rep_rad_scale <br />
|Scalar multiplier of the radii for the repulsive portion of the VDW energy component ONLY <br />
|1<br />
|-<br />
|fps_score_use_distance_dependent_dielectric <br />
|Distance dependent dielectric switch <br />
|yes<br />
|-<br />
|fps_score_dielectric <br />
|Dielectric constant for electrostatic term <br />
|4.0<br />
|-<br />
|fps_score_vdw_scale <br />
|Scalar multiplier of vdw energy component <br />
|1<br />
|-<br />
|fps_score_es_scale <br />
|Scalar multiplier of es energy component <br />
|1<br />
|-<br />
|fps_score_hb_scale <br />
|Scalar multiplier of hb energy component <br />
|0<br />
|-<br />
|fps_score_internal_scale <br />
|Scalar multiplier of internal energy component <br />
|0<br />
|-<br />
|fps_score_fp_vwd_scale <br />
|Scalar multiplier of vdw footprint component <br />
|0<br />
|-<br />
|fps_score_fp_es_scale <br />
|Scalar multiplier of es footprint component <br />
|0<br />
|-<br />
|fps_score_fp_hb_scale <br />
|Scalar multiplier of hb footprint component <br />
|0<br />
|-<br />
|}<br />
<br />
===Footprint Similarity Score Output Components===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
|Footprint_similarity_score<br />
|sum of the van der Waals, electostatic, and hbond footprint similarity scores<br />
|-<br />
|FPS_vdw_energy<br />
|VDW interaction between ligand and receptor<br />
|-<br />
|FPS_es_energy<br />
|ES interaction between the ligand and receptor<br />
|-<br />
|FPS_num_hbond<br />
|number of hydrogen bonds<br />
|-<br />
|FPS_vdw+es_energy<br />
|sum of the van der Waals and electrostatic components<br />
|-<br />
|FPS_vdw_fps<br />
|vdw footprint similarity score<br />
|-<br />
|FPS_es_fps<br />
|ES footprint similarity score<br />
|-<br />
|FPS_hb_fps<br />
|hbond footprint similarity score<br />
|-<br />
|FPS_vdw_fp_numres<br />
|number of residues in the receptor considered during the calculation<br />
|-<br />
|FPS_es_fp_numres<br />
|number of residues in the receptor considered during the calculation<br />
|-<br />
|FPS_hb_fp_numres<br />
|number of residues in the receptor considered during the calculation<br />
|-<br />
|}</div>Lprentishttps://ringo.ams.stonybrook.edu/index.php?title=Scoring_Functions&diff=13087Scoring Functions2020-04-14T18:12:59Z<p>Lprentis: /* Footprint Similarity Score */</p>
<hr />
<div>DOCK uses several types of scoring functions to discriminate among orientations and molecules. Scoring is requested using the score_molecules parameter. A large portion of scoring functions can be called through descriptor score (but not all). Those with descriptor score functionality will be denoted as such. <br />
<br />
==Grid-Based Score== <br />
DOCK needs a fast scoring function to evaluate poses rapidly during growth. The energy grid is used for this. The grid stores the non-bonded Molecular Mechanics Potential of the receptor at each grid point. <br />
[[Image:Mm-equation.png|450px|center]]<br />
'''Grid can be called under descriptor score but it is suggested to not mix grid-based and cartesian space as that will dramatically increase computing time.'''<br />
===Grid Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
| grid_score_primary<br />
| Does the user want to perform grid-based energy scoring as the primary scoring function? || yes- <br />
|-<br />
| grid_score_rep_rad_scale<br />
| Scalar multiplier of the radii for the repulsive portion of the VDW energy component only when grid score is turned on || 1.0<br />
|-<br />
| grid_score_vdw_scale <br />
| Scalar multiplier of the VDW energy component || 1<br />
|-<br />
| grid_score_turn_off_vdw <br />
| A flag to turn off vdw portion of scoring function when grid score vdw scale = 0 || yes<br />
|-<br />
| grid_score_es_scale <br />
| Flag to scale up or down the es portion of the scoring function when es scale is turned on || 1<br />
|-<br />
| grid_score_turn_off_es <br />
| A flag to turn off es portion of scoring function when grid score es scale = 0 || yes<br />
|-<br />
| grid_score_grid_prefix <br />
| The prefix to the grid files containing the desired nrg/bmp grid || grid<br />
|-<br />
|}<br />
<br />
===Grid Score Output Components===<br />
These values will be printed in the header of the mol2 file post DOCK process.<br />
<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
| Grid_score<br />
| Sum of the VDW and ES interactions <br />
|-<br />
| Grid_vdw_energy<br />
| VDW interaction between the ligand grid<br />
|-<br />
| Grid_es_energy<br />
| ES interaction betweent eh ligand and grid<br />
|}<br />
<br />
== Continuous/DOCK Cartesian Energy Score==<br />
Continuous scoring may be used to evaluate a ligand:receptor complex without the investment of a grid calculation, or to perform a more detailed calculation without the numerical approximation of the grid. '''Continuous score is implemented under Descriptor Score as well'''. Continuous score is a cartesian based score and can be combined with other Cartesian based scores with very little computational expense.<br />
<br />
===Continuous/DCE Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
|continuous_score_primary<br />
| Does the user want to perform continuous non-grid scoring as the primary scoring function?<br />
| no<br />
|-<br />
|continuous_score_secondary <br />
| Does the user want to perform continuous non-grid scoring as the secondary scoring function? <br />
|no<br />
|-<br />
|cont_score_rec_filename <br />
|File that contains receptor coordinates <br />
|receptor.mol2<br />
|-<br />
|cont_score_att_exp <br />
|VDW Lennard-Jones potential attractive exponent <br />
|6<br />
|-<br />
|cont_score_rep_exp <br />
|VDW Lennard-Jones potential repulsive exponent <br />
|12<br />
|-<br />
|cont_score_rep_rad_scale <br />
|Scalar multiplier of the radii for the repulsive portion of the vdw energy component only <br />
|1.0<br />
|-<br />
|cont_score_use_dist_dep_dielectric <br />
|Distance dependent dielectric switch <br />
|yes<br />
|-<br />
|cont_score_dielectric <br />
|Dielectric constant for the electrostatic term <br />
|<br />
|- <br />
|cont_score_vdw_scale <br />
|Scalar multiplier of vdw energy component <br />
|1 <br />
|-<br />
|cont_score_vdw_scale <br />
|Flag to turn off vdw portion of the scoring function when cont_score_vdw_scale=0 <br />
|yes<br />
|- <br />
|cont_score_es_scale <br />
|Scalar multiplier of electrostatic energy component <br />
|1.0 <br />
|-<br />
|cont_score_turn_off_es <br />
|Flag to turn off es portion of the scoring function when cont_score_es_scale = 0 <br />
|yes<br />
|-<br />
|}<br />
<br />
===Continuous/DCE Score Output Components===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
|Continuous-score<br />
|sum of the van der Waals and electrostatic interactions<br />
|-<br />
|Continuous_vdw_energy<br />
|VDW interaction between ligand and receptor<br />
|-<br />
|Continuous_es_energy<br />
|ES interaction between the ligand and receptor<br />
|-<br />
|}<br />
<br />
==Footprint Similarity Score==<br />
The Footprint Similarity Score is a scoring function that calculates intermolecular hydrogen bonds and footprint comparisons, in addition to standard intermolecular energies (VDW and ES). <br />
<br />
Intermolecular Energies (VDW, ES) are calculated the same way as in Continuous Score.<br />
<br />
A geometric definition of Hydrogen bonds is employed. We define 3 atoms XD, HD, and XA as the heavy atom donor, donated hydrogen, and heavy atom acceptor, respectively. There is a hydrogen bond present if the following two conditions are met:<br />
<br />
# The distance between HD and XA is less than or equal to 2.5 angstroms;<br />
# The angle defined by XD, HD, and XA is between 120 and 180 degrees.<br />
<br />
Footprints are a per-residue decomposition of interactions between the ligand and the receptor. This can be performed for all three terms VDW, ES, HB.<br />
Two footprints can be compared in three ways: Standard Euclidean, Normalized Euclidean, Pearson Correlation.<br />
<br />
Footprints are used to gauge how similar two poses or two molecules are to one-another. For applications to virtual screening applications a reference is required.<br />
<br />
There are to choices for a reference:<br />
<br />
# One can give a mol2 file containing a reference molecule, and footprints will be calculated.<br />
# One can pass a text file containing VDW, ES, and H-bond footprints. <br />
There are different choices for selection of residues:<br />
<br />
# All residues.<br />
# Residues chosen using a threshold (union of the sets of reference and pose). The VDW, ES, and HB footprints may have different residues chosen in this case.<br />
# Selected residues.<br />
<br />
Note that for (2) and (3) the remaining residue interaction may be placed in a remainder value included in the footprint.<br />
<br />
'''Footprint Similarity Score can be called under Descriptor Score.'''<br />
<br />
===Footprint Similarity Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
|footprint_similarity_score_primary <br />
|Flag to perform footprint scoring as the primary scoring function <br />
|no<br />
|-<br />
|footprint_similarity_score_secondary <br />
|Flag to perform footprint scoring as the secondary scoring function. <br />
|no<br />
|-<br />
|fps_score_use_footprint_reference_mol2 <br />
|Use a molecule to calculate footprint reference. <br />
|no<br />
|-<br />
|fps_score_footprint_reference_mol2_filename <br />
|Path to the reference mol2 file - only used when footprint reference mol2 is turned on. <br />
|ligand_footprint.mol2<br />
|-<br />
|fps_score_use_footprint_reference_txt <br />
|Use a pre-calculated footprint reference in text format. <br />
|no<br />
|-<br />
|fps_score_footprint_reference_txt_filename <br />
|Path to the reference txt file - only used when footprint reference txt is turned on. <br />
|ligand_footprint.txt<br />
|-<br />
|fps_score_foot_compare_type <br />
|Footprint similarity calculation methods (Options: Euclidean, Pearson). If Pearson, the correlation coefficient as the metric to compare the footprints. When the value is 1 then there is perfect agreement between the two footprints. WHen the value is 0 then there is poor agreement between the two footprints. If Euclidean, the Euclidean distance as the metric to compare the footprints. When the value is 0 then there is perfect agreement btween the two footprints. As the agreement gets worse between the two footprints the value increases. <br />
|Euclidean<br />
|-<br />
|fps_score_normalize_foot <br />
|normalization is used only with Euclidean distance. <br />
|no<br />
|-<br />
|fps_score_foot_comp_all_residue <br />
|If yes all residues are used for calculating the footprint. <br />
|yes<br />
|-<br />
|fps_score_choose_foot_range_type <br />
|User can use to determine the type of the range of the footprint by either specifying a residue range or defining a threshold. If specify_range, the user chooses to use a residue range and all footprints will be evaluated only on this residue range. First residue id = 1 not 0. If threshold, the user chose to use a residue range that is defined by only residues that have magnitudes that exceed the specified thresholds. (Options: specify_range, threshold) <br />
|specify_range<br />
|-<br />
|fps_score_vdw_threshold <br />
|Specify threshold for van der Waals energy, when threshold is turned on. <br />
|1<br />
|-<br />
|fps_score_es_threshold <br />
|Specify threshold for electrostatic energy, when threshold is turned on. <br />
|1<br />
|-<br />
|fps_score_hb_threshold <br />
|specify threshold for hydrogen bonds (integers). 0.5 means that all none zeros are used, when threshold is turned on. <br />
|0.5<br />
|-<br />
|fps_score_use_remainder <br />
|Interaction remainder is all remaining residues not included individually <br />
|yes<br />
|-<br />
|fps_score_rec_filename <br />
|File that contains receptor coordinates <br />
|receptor.mol2<br />
|-<br />
|fps_score_att_exp <br />
|VDW Lennard-Jones potential attractive exponent <br />
|6<br />
|-<br />
|fps_score_rep_exp <br />
|VDW Lennard-Jones potential repulsive exponent <br />
|12<br />
|-<br />
|fps_score_rep_rad_scale <br />
|Scalar multiplier of the radii for the repulsive portion of the VDW energy component ONLY <br />
|1<br />
|-<br />
|fps_score_use_distance_dependent_dielectric <br />
|Distance dependent dielectric switch <br />
|yes<br />
|-<br />
|fps_score_dielectric <br />
|Dielectric constant for electrostatic term <br />
|4.0<br />
|-<br />
|fps_score_vdw_scale <br />
|Scalar multiplier of vdw energy component <br />
|1<br />
|-<br />
|fps_score_es_scale <br />
|Scalar multiplier of es energy component <br />
|1<br />
|-<br />
|fps_score_hb_scale <br />
|Scalar multiplier of hb energy component <br />
|0<br />
|-<br />
|fps_score_internal_scale <br />
|Scalar multiplier of internal energy component <br />
|0<br />
|-<br />
|fps_score_fp_vwd_scale <br />
|Scalar multiplier of vdw footprint component <br />
|0<br />
|-<br />
|fps_score_fp_es_scale <br />
|Scalar multiplier of es footprint component <br />
|0<br />
|-<br />
|fps_score_fp_hb_scale <br />
|Scalar multiplier of hb footprint component <br />
|0<br />
|-<br />
|}<br />
<br />
===Footprint Similarity Score Output Components===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
|Footprint_similarity_score<br />
|sum of the van der Waals, electostatic, and hbond footprint similarity scores<br />
|-<br />
|FPS_vdw_energy<br />
|VDW interaction between ligand and receptor<br />
|-<br />
|FPS_es_energy<br />
|ES interaction between the ligand and receptor<br />
|-<br />
|FPS_num_hbond<br />
|number of hydrogen bonds<br />
|-<br />
|FPS_vdw+es_energy<br />
|sum of the van der Waals and electrostatic components<br />
|-<br />
|FPS_vdw_fps<br />
|vdw footprint similarity score<br />
|-<br />
|FPS_es_fps<br />
|ES footprint similarity score<br />
|-<br />
|FPS_hb_fps<br />
|hbond footprint similarity score<br />
|-<br />
|FPS_vdw_fp_numres<br />
|number of residues in the receptor considered during the calculation<br />
|-<br />
|FPS_es_fp_numres<br />
|number of residues in the receptor considered during the calculation<br />
|-<br />
|FPS_hb_fp_numres<br />
|number of residues in the receptor considered during the calculation<br />
|-<br />
|}<br />
|}</div>Lprentishttps://ringo.ams.stonybrook.edu/index.php?title=Scoring_Functions&diff=13086Scoring Functions2020-04-14T18:04:49Z<p>Lprentis: </p>
<hr />
<div>DOCK uses several types of scoring functions to discriminate among orientations and molecules. Scoring is requested using the score_molecules parameter. A large portion of scoring functions can be called through descriptor score (but not all). Those with descriptor score functionality will be denoted as such. <br />
<br />
==Grid-Based Score== <br />
DOCK needs a fast scoring function to evaluate poses rapidly during growth. The energy grid is used for this. The grid stores the non-bonded Molecular Mechanics Potential of the receptor at each grid point. <br />
[[Image:Mm-equation.png|450px|center]]<br />
'''Grid can be called under descriptor score but it is suggested to not mix grid-based and cartesian space as that will dramatically increase computing time.'''<br />
===Grid Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
| grid_score_primary<br />
| Does the user want to perform grid-based energy scoring as the primary scoring function? || yes- <br />
|-<br />
| grid_score_rep_rad_scale<br />
| Scalar multiplier of the radii for the repulsive portion of the VDW energy component only when grid score is turned on || 1.0<br />
|-<br />
| grid_score_vdw_scale <br />
| Scalar multiplier of the VDW energy component || 1<br />
|-<br />
| grid_score_turn_off_vdw <br />
| A flag to turn off vdw portion of scoring function when grid score vdw scale = 0 || yes<br />
|-<br />
| grid_score_es_scale <br />
| Flag to scale up or down the es portion of the scoring function when es scale is turned on || 1<br />
|-<br />
| grid_score_turn_off_es <br />
| A flag to turn off es portion of scoring function when grid score es scale = 0 || yes<br />
|-<br />
| grid_score_grid_prefix <br />
| The prefix to the grid files containing the desired nrg/bmp grid || grid<br />
|-<br />
|}<br />
<br />
===Grid Score Output Components===<br />
These values will be printed in the header of the mol2 file post DOCK process.<br />
<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
| Grid_score<br />
| Sum of the VDW and ES interactions <br />
|-<br />
| Grid_vdw_energy<br />
| VDW interaction between the ligand grid<br />
|-<br />
| Grid_es_energy<br />
| ES interaction betweent eh ligand and grid<br />
|}<br />
<br />
== Continuous/DOCK Cartesian Energy Score==<br />
Continuous scoring may be used to evaluate a ligand:receptor complex without the investment of a grid calculation, or to perform a more detailed calculation without the numerical approximation of the grid. '''Continuous score is implemented under Descriptor Score as well'''. Continuous score is a cartesian based score and can be combined with other Cartesian based scores with very little computational expense.<br />
<br />
===Continuous/DCE Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
|continuous_score_primary<br />
| Does the user want to perform continuous non-grid scoring as the primary scoring function?<br />
| no<br />
|-<br />
|continuous_score_secondary <br />
| Does the user want to perform continuous non-grid scoring as the secondary scoring function? <br />
|no<br />
|-<br />
|cont_score_rec_filename <br />
|File that contains receptor coordinates <br />
|receptor.mol2<br />
|-<br />
|cont_score_att_exp <br />
|VDW Lennard-Jones potential attractive exponent <br />
|6<br />
|-<br />
|cont_score_rep_exp <br />
|VDW Lennard-Jones potential repulsive exponent <br />
|12<br />
|-<br />
|cont_score_rep_rad_scale <br />
|Scalar multiplier of the radii for the repulsive portion of the vdw energy component only <br />
|1.0<br />
|-<br />
|cont_score_use_dist_dep_dielectric <br />
|Distance dependent dielectric switch <br />
|yes<br />
|-<br />
|cont_score_dielectric <br />
|Dielectric constant for the electrostatic term <br />
|<br />
|- <br />
|cont_score_vdw_scale <br />
|Scalar multiplier of vdw energy component <br />
|1 <br />
|-<br />
|cont_score_vdw_scale <br />
|Flag to turn off vdw portion of the scoring function when cont_score_vdw_scale=0 <br />
|yes<br />
|- <br />
|cont_score_es_scale <br />
|Scalar multiplier of electrostatic energy component <br />
|1.0 <br />
|-<br />
|cont_score_turn_off_es <br />
|Flag to turn off es portion of the scoring function when cont_score_es_scale = 0 <br />
|yes<br />
|-<br />
|}<br />
<br />
===Continuous/DCE Score Output Components===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
|Continuous-score<br />
|sum of the van der Waals and electrostatic interactions<br />
|-<br />
|Continuous_vdw_energy<br />
|VDW interaction between ligand and receptor<br />
|-<br />
|Continuous_es_energy<br />
|ES interaction between the ligand and receptor<br />
|-<br />
|}<br />
<br />
==Footprint Similarity Score==<br />
The Footprint Similarity Score is a scoring function that calculates intermolecular hydrogen bonds and footprint comparisons, in addition to standard intermolecular energies (VDW and ES). <br />
<br />
Intermolecular Energies (VDW, ES) are calculated the same way as in Continuous Score.<br />
<br />
A geometric definition of Hydrogen bonds is employed. We define 3 atoms XD, HD, and XA as the heavy atom donor, donated hydrogen, and heavy atom acceptor, respectively. There is a hydrogen bond present if the following two conditions are met:<br />
<br />
# The distance between HD and XA is less than or equal to 2.5 angstroms;<br />
# The angle defined by XD, HD, and XA is between 120 and 180 degrees.<br />
<br />
Footprints are a per-residue decomposition of interactions between the ligand and the receptor. This can be performed for all three terms VDW, ES, HB.<br />
Two footprints can be compared in three ways: Standard Euclidean, Normalized Euclidean, Pearson Correlation.<br />
<br />
Footprints are used to gauge how similar two poses or two molecules are to one-another. For applications to virtual screening applications a reference is required.<br />
<br />
There are to choices for a reference:<br />
<br />
# One can give a mol2 file containing a reference molecule, and footprints will be calculated.<br />
# One can pass a text file containing VDW, ES, and H-bond footprints. <br />
There are different choices for selection of residues:<br />
<br />
# All residues.<br />
# Residues chosen using a threshold (union of the sets of reference and pose). The VDW, ES, and HB footprints may have different residues chosen in this case.<br />
# Selected residues.<br />
<br />
Note that for (2) and (3) the remaining residue interaction may be placed in a remainder value included in the footprint.<br />
<br />
'''Footprint Similarity Score can be called under Descriptor Score.'''<br />
<br />
===Footprint Similarity Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
|footprint_similarity_score_primary <br />
|Flag to perform footprint scoring as the primary scoring function <br />
|no<br />
|-<br />
|footprint_similarity_score_secondary <br />
|Flag to perform footprint scoring as the secondary scoring function. <br />
|no<br />
|-<br />
|fps_score_use_footprint_reference_mol2 <br />
|Use a molecule to calculate footprint reference. <br />
|no<br />
|-<br />
|fps_score_footprint_reference_mol2_filename <br />
|Path to the reference mol2 file - only used when footprint reference mol2 is turned on. <br />
|ligand_footprint.mol2<br />
|-<br />
|fps_score_use_footprint_reference_txt <br />
|Use a pre-calculated footprint reference in text format. <br />
|no<br />
|-<br />
|fps_score_footprint_reference_txt_filename <br />
|Path to the reference txt file - only used when footprint reference txt is turned on. <br />
|ligand_footprint.txt<br />
|-<br />
|fps_score_foot_compare_type <br />
|Footprint similarity calculation methods (Options: Euclidean, Pearson). If Pearson, the correlation coefficient as the metric to compare the footprints. When the value is 1 then there is perfect agreement between the two footprints. WHen the value is 0 then there is poor agreement between the two footprints. If Euclidean, the Euclidean distance as the metric to compare the footprints. When the value is 0 then there is perfect agreement btween the two footprints. As the agreement gets worse between the two footprints the value increases. <br />
|Euclidean<br />
|-<br />
|fps_score_normalize_foot <br />
|normalization is used only with Euclidean distance. <br />
|no<br />
|-<br />
|fps_score_foot_comp_all_residue <br />
|If yes all residues are used for calculating the footprint. <br />
|yes<br />
|-<br />
|fps_score_choose_foot_range_type <br />
|User can use to determine the type of the range of the footprint by either specifying a residue range or defining a threshold. If specify_range, the user chooses to use a residue range and all footprints will be evaluated only on this residue range. First residue id = 1 not 0. If threshold, the user chose to use a residue range that is defined by only residues that have magnitudes that exceed the specified thresholds. (Options: specify_range, threshold) <br />
|specify_range<br />
|-<br />
|fps_score_vdw_threshold <br />
|Specify threshold for van der Waals energy, when threshold is turned on. <br />
|1<br />
|-<br />
|fps_score_es_threshold <br />
|Specify threshold for electrostatic energy, when threshold is turned on. <br />
|1<br />
|-<br />
|fps_score_hb_threshold <br />
|specify threshold for hydrogen bonds (integers). 0.5 means that all none zeros are used, when threshold is turned on. <br />
|0.5<br />
|-<br />
|fps_score_use_remainder <br />
|Interaction remainder is all remaining residues not included individually <br />
|yes<br />
|-<br />
|fps_score_rec_filename <br />
|File that contains receptor coordinates <br />
|receptor.mol2<br />
|-<br />
|fps_score_att_exp <br />
|VDW Lennard-Jones potential attractive exponent <br />
|6<br />
|-<br />
|fps_score_rep_exp <br />
|VDW Lennard-Jones potential repulsive exponent <br />
|12<br />
|-<br />
|fps_score_rep_rad_scale <br />
|Scalar multiplier of the radii for the repulsive portion of the VDW energy component ONLY <br />
|1<br />
|-<br />
|fps_score_use_distance_dependent_dielectric <br />
|Distance dependent dielectric switch <br />
|yes<br />
|-<br />
|fps_score_dielectric <br />
|Dielectric constant for electrostatic term <br />
|4.0<br />
|-<br />
|fps_score_vdw_scale <br />
|Scalar multiplier of vdw energy component <br />
|1<br />
|-<br />
|fps_score_es_scale <br />
|Scalar multiplier of es energy component <br />
|1<br />
|-<br />
|fps_score_hb_scale <br />
|Scalar multiplier of hb energy component <br />
|0<br />
|-<br />
|fps_score_internal_scale <br />
|Scalar multiplier of internal energy component <br />
|0<br />
|-<br />
|fps_score_fp_vwd_scale <br />
|Scalar multiplier of vdw footprint component <br />
|0<br />
|-<br />
|fps_score_fp_es_scale <br />
|Scalar multiplier of es footprint component <br />
|0<br />
|-<br />
|fps_score_fp_hb_scale <br />
|Scalar multiplier of hb footprint component <br />
|0<br />
|-<br />
|}</div>Lprentishttps://ringo.ams.stonybrook.edu/index.php?title=Scoring_Functions&diff=13085Scoring Functions2020-04-14T17:57:47Z<p>Lprentis: /* Footprint Similarity Score */</p>
<hr />
<div>DOCK uses several types of scoring functions to discriminate among orientations and molecules. Scoring is requested using the score_molecules parameter. A large portion of scoring functions can be called through descriptor score (but not all). Those with descriptor score functionality will be denoted as such. <br />
<br />
==Grid-Based Score== <br />
DOCK needs a fast scoring function to evaluate poses rapidly during growth. The energy grid is used for this. The grid stores the non-bonded Molecular Mechanics Potential of the receptor at each grid point. <br />
[[Image:Mm-equation.png|450px|center]]<br />
'''Grid can be called under descriptor score but it is suggested to not mix grid-based and cartesian space as that will dramatically increase computing time.'''<br />
===Grid Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
| grid_score_primary<br />
| Does the user want to perform grid-based energy scoring as the primary scoring function? || yes- <br />
|-<br />
| grid_score_rep_rad_scale<br />
| Scalar multiplier of the radii for the repulsive portion of the VDW energy component only when grid score is turned on || 1.0<br />
|-<br />
| grid_score_vdw_scale <br />
| Scalar multiplier of the VDW energy component || 1<br />
|-<br />
| grid_score_turn_off_vdw <br />
| A flag to turn off vdw portion of scoring function when grid score vdw scale = 0 || yes<br />
|-<br />
| grid_score_es_scale <br />
| Flag to scale up or down the es portion of the scoring function when es scale is turned on || 1<br />
|-<br />
| grid_score_turn_off_es <br />
| A flag to turn off es portion of scoring function when grid score es scale = 0 || yes<br />
|-<br />
| grid_score_grid_prefix <br />
| The prefix to the grid files containing the desired nrg/bmp grid || grid<br />
|-<br />
|}<br />
<br />
===Grid Score Output Components===<br />
These values will be printed in the header of the mol2 file post DOCK process.<br />
<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
| Grid_score<br />
| Sum of the VDW and ES interactions <br />
|-<br />
| Grid_vdw_energy<br />
| VDW interaction between the ligand grid<br />
|-<br />
| Grid_es_energy<br />
| ES interaction betweent eh ligand and grid<br />
|}<br />
<br />
== Continuous/DOCK Cartesian Energy Score==<br />
Continuous scoring may be used to evaluate a ligand:receptor complex without the investment of a grid calculation, or to perform a more detailed calculation without the numerical approximation of the grid. '''Continuous score is implemented under Descriptor Score as well'''. Continuous score is a cartesian based score and can be combined with other Cartesian based scores with very little computational expense.<br />
<br />
===Continuous/DCE Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
|continuous_score_primary<br />
| Does the user want to perform continuous non-grid scoring as the primary scoring function?<br />
| no<br />
|-<br />
|continuous_score_secondary <br />
| Does the user want to perform continuous non-grid scoring as the secondary scoring function? <br />
|no<br />
|-<br />
|cont_score_rec_filename <br />
|File that contains receptor coordinates <br />
|receptor.mol2<br />
|-<br />
|cont_score_att_exp <br />
|VDW Lennard-Jones potential attractive exponent <br />
|6<br />
|-<br />
|cont_score_rep_exp <br />
|VDW Lennard-Jones potential repulsive exponent <br />
|12<br />
|-<br />
|cont_score_rep_rad_scale <br />
|Scalar multiplier of the radii for the repulsive portion of the vdw energy component only <br />
|1.0<br />
|-<br />
|cont_score_use_dist_dep_dielectric <br />
|Distance dependent dielectric switch <br />
|yes<br />
|-<br />
|cont_score_dielectric <br />
|Dielectric constant for the electrostatic term <br />
|<br />
|- <br />
|cont_score_vdw_scale <br />
|Scalar multiplier of vdw energy component <br />
|1 <br />
|-<br />
|cont_score_vdw_scale <br />
|Flag to turn off vdw portion of the scoring function when cont_score_vdw_scale=0 <br />
|yes<br />
|- <br />
|cont_score_es_scale <br />
|Scalar multiplier of electrostatic energy component <br />
|1.0 <br />
|-<br />
|cont_score_turn_off_es <br />
|Flag to turn off es portion of the scoring function when cont_score_es_scale = 0 <br />
|yes<br />
|-<br />
|}<br />
<br />
===Continuous/DCE Score Output Components===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
|Continuous-score<br />
|sum of the van der Waals and electrostatic interactions<br />
|-<br />
|Continuous_vdw_energy<br />
|VDW interaction between ligand and receptor<br />
|-<br />
|Continuous_es_energy<br />
|ES interaction between the ligand and receptor<br />
|-<br />
|}<br />
<br />
==Footprint Similarity Score==<br />
The Footprint Similarity Score is a scoring function that calculates intermolecular hydrogen bonds and footprint comparisons, in addition to standard intermolecular energies (VDW and ES). <br />
<br />
Intermolecular Energies (VDW, ES) are calculated the same way as in Continuous Score.<br />
<br />
A geometric definition of Hydrogen bonds is employed. We define 3 atoms XD, HD, and XA as the heavy atom donor, donated hydrogen, and heavy atom acceptor, respectively. There is a hydrogen bond present if the following two conditions are met:<br />
<br />
# The distance between HD and XA is less than or equal to 2.5 angstroms;<br />
# The angle defined by XD, HD, and XA is between 120 and 180 degrees.<br />
<br />
Footprints are a per-residue decomposition of interactions between the ligand and the receptor. This can be performed for all three terms VDW, ES, HB.<br />
Two footprints can be compared in three ways: Standard Euclidean, Normalized Euclidean, Pearson Correlation.<br />
<br />
Footprints are used to gauge how similar two poses or two molecules are to one-another. For applications to virtual screening applications a reference is required.<br />
<br />
There are to choices for a reference:<br />
<br />
# One can give a mol2 file containing a reference molecule, and footprints will be calculated.<br />
# One can pass a text file containing VDW, ES, and H-bond footprints. <br />
There are different choices for selection of residues:<br />
<br />
# All residues.<br />
# Residues chosen using a threshold (union of the sets of reference and pose). The VDW, ES, and HB footprints may have different residues chosen in this case.<br />
# Selected residues.<br />
<br />
Note that for (2) and (3) the remaining residue interaction may be placed in a remainder value included in the footprint.<br />
<br />
'''Footprint Similarity Score can be called under Descriptor Score.'''</div>Lprentishttps://ringo.ams.stonybrook.edu/index.php?title=Scoring_Functions&diff=13084Scoring Functions2020-04-14T17:57:11Z<p>Lprentis: /* Grid-Based Score */</p>
<hr />
<div>DOCK uses several types of scoring functions to discriminate among orientations and molecules. Scoring is requested using the score_molecules parameter. A large portion of scoring functions can be called through descriptor score (but not all). Those with descriptor score functionality will be denoted as such. <br />
<br />
==Grid-Based Score== <br />
DOCK needs a fast scoring function to evaluate poses rapidly during growth. The energy grid is used for this. The grid stores the non-bonded Molecular Mechanics Potential of the receptor at each grid point. <br />
[[Image:Mm-equation.png|450px|center]]<br />
'''Grid can be called under descriptor score but it is suggested to not mix grid-based and cartesian space as that will dramatically increase computing time.'''<br />
===Grid Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
| grid_score_primary<br />
| Does the user want to perform grid-based energy scoring as the primary scoring function? || yes- <br />
|-<br />
| grid_score_rep_rad_scale<br />
| Scalar multiplier of the radii for the repulsive portion of the VDW energy component only when grid score is turned on || 1.0<br />
|-<br />
| grid_score_vdw_scale <br />
| Scalar multiplier of the VDW energy component || 1<br />
|-<br />
| grid_score_turn_off_vdw <br />
| A flag to turn off vdw portion of scoring function when grid score vdw scale = 0 || yes<br />
|-<br />
| grid_score_es_scale <br />
| Flag to scale up or down the es portion of the scoring function when es scale is turned on || 1<br />
|-<br />
| grid_score_turn_off_es <br />
| A flag to turn off es portion of scoring function when grid score es scale = 0 || yes<br />
|-<br />
| grid_score_grid_prefix <br />
| The prefix to the grid files containing the desired nrg/bmp grid || grid<br />
|-<br />
|}<br />
<br />
===Grid Score Output Components===<br />
These values will be printed in the header of the mol2 file post DOCK process.<br />
<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
| Grid_score<br />
| Sum of the VDW and ES interactions <br />
|-<br />
| Grid_vdw_energy<br />
| VDW interaction between the ligand grid<br />
|-<br />
| Grid_es_energy<br />
| ES interaction betweent eh ligand and grid<br />
|}<br />
<br />
== Continuous/DOCK Cartesian Energy Score==<br />
Continuous scoring may be used to evaluate a ligand:receptor complex without the investment of a grid calculation, or to perform a more detailed calculation without the numerical approximation of the grid. '''Continuous score is implemented under Descriptor Score as well'''. Continuous score is a cartesian based score and can be combined with other Cartesian based scores with very little computational expense.<br />
<br />
===Continuous/DCE Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
|continuous_score_primary<br />
| Does the user want to perform continuous non-grid scoring as the primary scoring function?<br />
| no<br />
|-<br />
|continuous_score_secondary <br />
| Does the user want to perform continuous non-grid scoring as the secondary scoring function? <br />
|no<br />
|-<br />
|cont_score_rec_filename <br />
|File that contains receptor coordinates <br />
|receptor.mol2<br />
|-<br />
|cont_score_att_exp <br />
|VDW Lennard-Jones potential attractive exponent <br />
|6<br />
|-<br />
|cont_score_rep_exp <br />
|VDW Lennard-Jones potential repulsive exponent <br />
|12<br />
|-<br />
|cont_score_rep_rad_scale <br />
|Scalar multiplier of the radii for the repulsive portion of the vdw energy component only <br />
|1.0<br />
|-<br />
|cont_score_use_dist_dep_dielectric <br />
|Distance dependent dielectric switch <br />
|yes<br />
|-<br />
|cont_score_dielectric <br />
|Dielectric constant for the electrostatic term <br />
|<br />
|- <br />
|cont_score_vdw_scale <br />
|Scalar multiplier of vdw energy component <br />
|1 <br />
|-<br />
|cont_score_vdw_scale <br />
|Flag to turn off vdw portion of the scoring function when cont_score_vdw_scale=0 <br />
|yes<br />
|- <br />
|cont_score_es_scale <br />
|Scalar multiplier of electrostatic energy component <br />
|1.0 <br />
|-<br />
|cont_score_turn_off_es <br />
|Flag to turn off es portion of the scoring function when cont_score_es_scale = 0 <br />
|yes<br />
|-<br />
|}<br />
<br />
===Continuous/DCE Score Output Components===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
|Continuous-score<br />
|sum of the van der Waals and electrostatic interactions<br />
|-<br />
|Continuous_vdw_energy<br />
|VDW interaction between ligand and receptor<br />
|-<br />
|Continuous_es_energy<br />
|ES interaction between the ligand and receptor<br />
|-<br />
|}<br />
<br />
==Footprint Similarity Score==<br />
The Footprint Similarity Score is a scoring function that calculates intermolecular hydrogen bonds and footprint comparisons, in addition to standard intermolecular energies (VDW and ES). <br />
<br />
Intermolecular Energies (VDW, ES) are calculated the same way as in Continuous Score.<br />
<br />
A geometric definition of Hydrogen bonds is employed. We define 3 atoms XD, HD, and XA as the heavy atom donor, donated hydrogen, and heavy atom acceptor, respectively. There is a hydrogen bond present if the following two conditions are met:<br />
<br />
# The distance between HD and XA is less than or equal to 2.5 angstroms;<br />
# The angle defined by XD, HD, and XA is between 120 and 180 degrees.<br />
<br />
Footprints are a per-residue decomposition of interactions between the ligand and the receptor. This can be performed for all three terms VDW, ES, HB.<br />
Two footprints can be compared in three ways: Standard Euclidean, Normalized Euclidean, Pearson Correlation.<br />
<br />
Footprints are used to gauge how similar two poses or two molecules are to one-another. For applications to virtual screening applications a reference is required.<br />
<br />
There are to choices for a reference:<br />
<br />
# One can give a mol2 file containing a reference molecule, and footprints will be calculated.<br />
# One can pass a text file containing VDW, ES, and H-bond footprints. <br />
There are different choices for selection of residues:<br />
<br />
# All residues.<br />
# Residues chosen using a threshold (union of the sets of reference and pose). The VDW, ES, and HB footprints may have different residues chosen in this case.<br />
# Selected residues.<br />
<br />
Note that for (2) and (3) the remaining residue interaction may be placed in a remainder value included in the footprint.</div>Lprentishttps://ringo.ams.stonybrook.edu/index.php?title=Scoring_Functions&diff=13083Scoring Functions2020-04-14T17:56:56Z<p>Lprentis: /* Continuous/DOCK Cartesian Energy Score */</p>
<hr />
<div>DOCK uses several types of scoring functions to discriminate among orientations and molecules. Scoring is requested using the score_molecules parameter. A large portion of scoring functions can be called through descriptor score (but not all). Those with descriptor score functionality will be denoted as such. <br />
<br />
==Grid-Based Score== <br />
DOCK needs a fast scoring function to evaluate poses rapidly during growth. The energy grid is used for this. The grid stores the non-bonded Molecular Mechanics Potential of the receptor at each grid point. <br />
[[Image:Mm-equation.png|450px|center]]<br />
Grid can be called under descriptor score but it is suggested to not mix grid-based and cartesian space as that will dramatically increase computing time.<br />
===Grid Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
| grid_score_primary<br />
| Does the user want to perform grid-based energy scoring as the primary scoring function? || yes- <br />
|-<br />
| grid_score_rep_rad_scale<br />
| Scalar multiplier of the radii for the repulsive portion of the VDW energy component only when grid score is turned on || 1.0<br />
|-<br />
| grid_score_vdw_scale <br />
| Scalar multiplier of the VDW energy component || 1<br />
|-<br />
| grid_score_turn_off_vdw <br />
| A flag to turn off vdw portion of scoring function when grid score vdw scale = 0 || yes<br />
|-<br />
| grid_score_es_scale <br />
| Flag to scale up or down the es portion of the scoring function when es scale is turned on || 1<br />
|-<br />
| grid_score_turn_off_es <br />
| A flag to turn off es portion of scoring function when grid score es scale = 0 || yes<br />
|-<br />
| grid_score_grid_prefix <br />
| The prefix to the grid files containing the desired nrg/bmp grid || grid<br />
|-<br />
|}<br />
<br />
===Grid Score Output Components===<br />
These values will be printed in the header of the mol2 file post DOCK process.<br />
<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
| Grid_score<br />
| Sum of the VDW and ES interactions <br />
|-<br />
| Grid_vdw_energy<br />
| VDW interaction between the ligand grid<br />
|-<br />
| Grid_es_energy<br />
| ES interaction betweent eh ligand and grid<br />
|}<br />
<br />
== Continuous/DOCK Cartesian Energy Score==<br />
Continuous scoring may be used to evaluate a ligand:receptor complex without the investment of a grid calculation, or to perform a more detailed calculation without the numerical approximation of the grid. '''Continuous score is implemented under Descriptor Score as well'''. Continuous score is a cartesian based score and can be combined with other Cartesian based scores with very little computational expense.<br />
<br />
===Continuous/DCE Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
|continuous_score_primary<br />
| Does the user want to perform continuous non-grid scoring as the primary scoring function?<br />
| no<br />
|-<br />
|continuous_score_secondary <br />
| Does the user want to perform continuous non-grid scoring as the secondary scoring function? <br />
|no<br />
|-<br />
|cont_score_rec_filename <br />
|File that contains receptor coordinates <br />
|receptor.mol2<br />
|-<br />
|cont_score_att_exp <br />
|VDW Lennard-Jones potential attractive exponent <br />
|6<br />
|-<br />
|cont_score_rep_exp <br />
|VDW Lennard-Jones potential repulsive exponent <br />
|12<br />
|-<br />
|cont_score_rep_rad_scale <br />
|Scalar multiplier of the radii for the repulsive portion of the vdw energy component only <br />
|1.0<br />
|-<br />
|cont_score_use_dist_dep_dielectric <br />
|Distance dependent dielectric switch <br />
|yes<br />
|-<br />
|cont_score_dielectric <br />
|Dielectric constant for the electrostatic term <br />
|<br />
|- <br />
|cont_score_vdw_scale <br />
|Scalar multiplier of vdw energy component <br />
|1 <br />
|-<br />
|cont_score_vdw_scale <br />
|Flag to turn off vdw portion of the scoring function when cont_score_vdw_scale=0 <br />
|yes<br />
|- <br />
|cont_score_es_scale <br />
|Scalar multiplier of electrostatic energy component <br />
|1.0 <br />
|-<br />
|cont_score_turn_off_es <br />
|Flag to turn off es portion of the scoring function when cont_score_es_scale = 0 <br />
|yes<br />
|-<br />
|}<br />
<br />
===Continuous/DCE Score Output Components===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
|Continuous-score<br />
|sum of the van der Waals and electrostatic interactions<br />
|-<br />
|Continuous_vdw_energy<br />
|VDW interaction between ligand and receptor<br />
|-<br />
|Continuous_es_energy<br />
|ES interaction between the ligand and receptor<br />
|-<br />
|}<br />
<br />
==Footprint Similarity Score==<br />
The Footprint Similarity Score is a scoring function that calculates intermolecular hydrogen bonds and footprint comparisons, in addition to standard intermolecular energies (VDW and ES). <br />
<br />
Intermolecular Energies (VDW, ES) are calculated the same way as in Continuous Score.<br />
<br />
A geometric definition of Hydrogen bonds is employed. We define 3 atoms XD, HD, and XA as the heavy atom donor, donated hydrogen, and heavy atom acceptor, respectively. There is a hydrogen bond present if the following two conditions are met:<br />
<br />
# The distance between HD and XA is less than or equal to 2.5 angstroms;<br />
# The angle defined by XD, HD, and XA is between 120 and 180 degrees.<br />
<br />
Footprints are a per-residue decomposition of interactions between the ligand and the receptor. This can be performed for all three terms VDW, ES, HB.<br />
Two footprints can be compared in three ways: Standard Euclidean, Normalized Euclidean, Pearson Correlation.<br />
<br />
Footprints are used to gauge how similar two poses or two molecules are to one-another. For applications to virtual screening applications a reference is required.<br />
<br />
There are to choices for a reference:<br />
<br />
# One can give a mol2 file containing a reference molecule, and footprints will be calculated.<br />
# One can pass a text file containing VDW, ES, and H-bond footprints. <br />
There are different choices for selection of residues:<br />
<br />
# All residues.<br />
# Residues chosen using a threshold (union of the sets of reference and pose). The VDW, ES, and HB footprints may have different residues chosen in this case.<br />
# Selected residues.<br />
<br />
Note that for (2) and (3) the remaining residue interaction may be placed in a remainder value included in the footprint.</div>Lprentishttps://ringo.ams.stonybrook.edu/index.php?title=Scoring_Functions&diff=13082Scoring Functions2020-04-14T17:56:19Z<p>Lprentis: /* Continuous/DOCK Cartesian Energy Score */</p>
<hr />
<div>DOCK uses several types of scoring functions to discriminate among orientations and molecules. Scoring is requested using the score_molecules parameter. A large portion of scoring functions can be called through descriptor score (but not all). Those with descriptor score functionality will be denoted as such. <br />
<br />
==Grid-Based Score== <br />
DOCK needs a fast scoring function to evaluate poses rapidly during growth. The energy grid is used for this. The grid stores the non-bonded Molecular Mechanics Potential of the receptor at each grid point. <br />
[[Image:Mm-equation.png|450px|center]]<br />
Grid can be called under descriptor score but it is suggested to not mix grid-based and cartesian space as that will dramatically increase computing time.<br />
===Grid Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
| grid_score_primary<br />
| Does the user want to perform grid-based energy scoring as the primary scoring function? || yes- <br />
|-<br />
| grid_score_rep_rad_scale<br />
| Scalar multiplier of the radii for the repulsive portion of the VDW energy component only when grid score is turned on || 1.0<br />
|-<br />
| grid_score_vdw_scale <br />
| Scalar multiplier of the VDW energy component || 1<br />
|-<br />
| grid_score_turn_off_vdw <br />
| A flag to turn off vdw portion of scoring function when grid score vdw scale = 0 || yes<br />
|-<br />
| grid_score_es_scale <br />
| Flag to scale up or down the es portion of the scoring function when es scale is turned on || 1<br />
|-<br />
| grid_score_turn_off_es <br />
| A flag to turn off es portion of scoring function when grid score es scale = 0 || yes<br />
|-<br />
| grid_score_grid_prefix <br />
| The prefix to the grid files containing the desired nrg/bmp grid || grid<br />
|-<br />
|}<br />
<br />
===Grid Score Output Components===<br />
These values will be printed in the header of the mol2 file post DOCK process.<br />
<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
| Grid_score<br />
| Sum of the VDW and ES interactions <br />
|-<br />
| Grid_vdw_energy<br />
| VDW interaction between the ligand grid<br />
|-<br />
| Grid_es_energy<br />
| ES interaction betweent eh ligand and grid<br />
|}<br />
<br />
== Continuous/DOCK Cartesian Energy Score==<br />
Continuous scoring may be used to evaluate a ligand:receptor complex without the investment of a grid calculation, or to perform a more detailed calculation without the numerical approximation of the grid. [[Continuous score is implemented under Descriptor Score as well]]. Continuous score is a cartesian based score and can be combined with other Cartesian based scores with very little computational expense.<br />
<br />
===Continuous/DCE Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
|continuous_score_primary<br />
| Does the user want to perform continuous non-grid scoring as the primary scoring function?<br />
| no<br />
|-<br />
|continuous_score_secondary <br />
| Does the user want to perform continuous non-grid scoring as the secondary scoring function? <br />
|no<br />
|-<br />
|cont_score_rec_filename <br />
|File that contains receptor coordinates <br />
|receptor.mol2<br />
|-<br />
|cont_score_att_exp <br />
|VDW Lennard-Jones potential attractive exponent <br />
|6<br />
|-<br />
|cont_score_rep_exp <br />
|VDW Lennard-Jones potential repulsive exponent <br />
|12<br />
|-<br />
|cont_score_rep_rad_scale <br />
|Scalar multiplier of the radii for the repulsive portion of the vdw energy component only <br />
|1.0<br />
|-<br />
|cont_score_use_dist_dep_dielectric <br />
|Distance dependent dielectric switch <br />
|yes<br />
|-<br />
|cont_score_dielectric <br />
|Dielectric constant for the electrostatic term <br />
|<br />
|- <br />
|cont_score_vdw_scale <br />
|Scalar multiplier of vdw energy component <br />
|1 <br />
|-<br />
|cont_score_vdw_scale <br />
|Flag to turn off vdw portion of the scoring function when cont_score_vdw_scale=0 <br />
|yes<br />
|- <br />
|cont_score_es_scale <br />
|Scalar multiplier of electrostatic energy component <br />
|1.0 <br />
|-<br />
|cont_score_turn_off_es <br />
|Flag to turn off es portion of the scoring function when cont_score_es_scale = 0 <br />
|yes<br />
|-<br />
|}<br />
<br />
===Continuous/DCE Score Output Components===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
|Continuous-score<br />
|sum of the van der Waals and electrostatic interactions<br />
|-<br />
|Continuous_vdw_energy<br />
|VDW interaction between ligand and receptor<br />
|-<br />
|Continuous_es_energy<br />
|ES interaction between the ligand and receptor<br />
|-<br />
|}<br />
<br />
==Footprint Similarity Score==<br />
The Footprint Similarity Score is a scoring function that calculates intermolecular hydrogen bonds and footprint comparisons, in addition to standard intermolecular energies (VDW and ES). <br />
<br />
Intermolecular Energies (VDW, ES) are calculated the same way as in Continuous Score.<br />
<br />
A geometric definition of Hydrogen bonds is employed. We define 3 atoms XD, HD, and XA as the heavy atom donor, donated hydrogen, and heavy atom acceptor, respectively. There is a hydrogen bond present if the following two conditions are met:<br />
<br />
# The distance between HD and XA is less than or equal to 2.5 angstroms;<br />
# The angle defined by XD, HD, and XA is between 120 and 180 degrees.<br />
<br />
Footprints are a per-residue decomposition of interactions between the ligand and the receptor. This can be performed for all three terms VDW, ES, HB.<br />
Two footprints can be compared in three ways: Standard Euclidean, Normalized Euclidean, Pearson Correlation.<br />
<br />
Footprints are used to gauge how similar two poses or two molecules are to one-another. For applications to virtual screening applications a reference is required.<br />
<br />
There are to choices for a reference:<br />
<br />
# One can give a mol2 file containing a reference molecule, and footprints will be calculated.<br />
# One can pass a text file containing VDW, ES, and H-bond footprints. <br />
There are different choices for selection of residues:<br />
<br />
# All residues.<br />
# Residues chosen using a threshold (union of the sets of reference and pose). The VDW, ES, and HB footprints may have different residues chosen in this case.<br />
# Selected residues.<br />
<br />
Note that for (2) and (3) the remaining residue interaction may be placed in a remainder value included in the footprint.</div>Lprentishttps://ringo.ams.stonybrook.edu/index.php?title=Scoring_Functions&diff=13081Scoring Functions2020-04-14T17:55:34Z<p>Lprentis: /* Footprint Similarity Score */</p>
<hr />
<div>DOCK uses several types of scoring functions to discriminate among orientations and molecules. Scoring is requested using the score_molecules parameter. A large portion of scoring functions can be called through descriptor score (but not all). Those with descriptor score functionality will be denoted as such. <br />
<br />
==Grid-Based Score== <br />
DOCK needs a fast scoring function to evaluate poses rapidly during growth. The energy grid is used for this. The grid stores the non-bonded Molecular Mechanics Potential of the receptor at each grid point. <br />
[[Image:Mm-equation.png|450px|center]]<br />
Grid can be called under descriptor score but it is suggested to not mix grid-based and cartesian space as that will dramatically increase computing time.<br />
===Grid Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
| grid_score_primary<br />
| Does the user want to perform grid-based energy scoring as the primary scoring function? || yes- <br />
|-<br />
| grid_score_rep_rad_scale<br />
| Scalar multiplier of the radii for the repulsive portion of the VDW energy component only when grid score is turned on || 1.0<br />
|-<br />
| grid_score_vdw_scale <br />
| Scalar multiplier of the VDW energy component || 1<br />
|-<br />
| grid_score_turn_off_vdw <br />
| A flag to turn off vdw portion of scoring function when grid score vdw scale = 0 || yes<br />
|-<br />
| grid_score_es_scale <br />
| Flag to scale up or down the es portion of the scoring function when es scale is turned on || 1<br />
|-<br />
| grid_score_turn_off_es <br />
| A flag to turn off es portion of scoring function when grid score es scale = 0 || yes<br />
|-<br />
| grid_score_grid_prefix <br />
| The prefix to the grid files containing the desired nrg/bmp grid || grid<br />
|-<br />
|}<br />
<br />
===Grid Score Output Components===<br />
These values will be printed in the header of the mol2 file post DOCK process.<br />
<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
| Grid_score<br />
| Sum of the VDW and ES interactions <br />
|-<br />
| Grid_vdw_energy<br />
| VDW interaction between the ligand grid<br />
|-<br />
| Grid_es_energy<br />
| ES interaction betweent eh ligand and grid<br />
|}<br />
<br />
== Continuous/DOCK Cartesian Energy Score==<br />
Continuous scoring may be used to evaluate a ligand:receptor complex without the investment of a grid calculation, or to perform a more detailed calculation without the numerical approximation of the grid. Continuous score is implemented under Descriptor Score as well. Continuous score is a cartesian based score and can be combined with other Cartesian based scores with very little computational expense.<br />
<br />
===Continuous/DCE Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
|continuous_score_primary<br />
| Does the user want to perform continuous non-grid scoring as the primary scoring function?<br />
| no<br />
|-<br />
|continuous_score_secondary <br />
| Does the user want to perform continuous non-grid scoring as the secondary scoring function? <br />
|no<br />
|-<br />
|cont_score_rec_filename <br />
|File that contains receptor coordinates <br />
|receptor.mol2<br />
|-<br />
|cont_score_att_exp <br />
|VDW Lennard-Jones potential attractive exponent <br />
|6<br />
|-<br />
|cont_score_rep_exp <br />
|VDW Lennard-Jones potential repulsive exponent <br />
|12<br />
|-<br />
|cont_score_rep_rad_scale <br />
|Scalar multiplier of the radii for the repulsive portion of the vdw energy component only <br />
|1.0<br />
|-<br />
|cont_score_use_dist_dep_dielectric <br />
|Distance dependent dielectric switch <br />
|yes<br />
|-<br />
|cont_score_dielectric <br />
|Dielectric constant for the electrostatic term <br />
|<br />
|- <br />
|cont_score_vdw_scale <br />
|Scalar multiplier of vdw energy component <br />
|1 <br />
|-<br />
|cont_score_vdw_scale <br />
|Flag to turn off vdw portion of the scoring function when cont_score_vdw_scale=0 <br />
|yes<br />
|- <br />
|cont_score_es_scale <br />
|Scalar multiplier of electrostatic energy component <br />
|1.0 <br />
|-<br />
|cont_score_turn_off_es <br />
|Flag to turn off es portion of the scoring function when cont_score_es_scale = 0 <br />
|yes<br />
|-<br />
|}<br />
<br />
===Continuous/DCE Score Output Components===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
|Continuous-score<br />
|sum of the van der Waals and electrostatic interactions<br />
|-<br />
|Continuous_vdw_energy<br />
|VDW interaction between ligand and receptor<br />
|-<br />
|Continuous_es_energy<br />
|ES interaction between the ligand and receptor<br />
|-<br />
|}<br />
<br />
==Footprint Similarity Score==<br />
The Footprint Similarity Score is a scoring function that calculates intermolecular hydrogen bonds and footprint comparisons, in addition to standard intermolecular energies (VDW and ES). <br />
<br />
Intermolecular Energies (VDW, ES) are calculated the same way as in Continuous Score.<br />
<br />
A geometric definition of Hydrogen bonds is employed. We define 3 atoms XD, HD, and XA as the heavy atom donor, donated hydrogen, and heavy atom acceptor, respectively. There is a hydrogen bond present if the following two conditions are met:<br />
<br />
# The distance between HD and XA is less than or equal to 2.5 angstroms;<br />
# The angle defined by XD, HD, and XA is between 120 and 180 degrees.<br />
<br />
Footprints are a per-residue decomposition of interactions between the ligand and the receptor. This can be performed for all three terms VDW, ES, HB.<br />
Two footprints can be compared in three ways: Standard Euclidean, Normalized Euclidean, Pearson Correlation.<br />
<br />
Footprints are used to gauge how similar two poses or two molecules are to one-another. For applications to virtual screening applications a reference is required.<br />
<br />
There are to choices for a reference:<br />
<br />
# One can give a mol2 file containing a reference molecule, and footprints will be calculated.<br />
# One can pass a text file containing VDW, ES, and H-bond footprints. <br />
There are different choices for selection of residues:<br />
<br />
# All residues.<br />
# Residues chosen using a threshold (union of the sets of reference and pose). The VDW, ES, and HB footprints may have different residues chosen in this case.<br />
# Selected residues.<br />
<br />
Note that for (2) and (3) the remaining residue interaction may be placed in a remainder value included in the footprint.</div>Lprentishttps://ringo.ams.stonybrook.edu/index.php?title=Scoring_Functions&diff=13080Scoring Functions2020-04-14T17:53:18Z<p>Lprentis: /* Footprint Similarity Score */</p>
<hr />
<div>DOCK uses several types of scoring functions to discriminate among orientations and molecules. Scoring is requested using the score_molecules parameter. A large portion of scoring functions can be called through descriptor score (but not all). Those with descriptor score functionality will be denoted as such. <br />
<br />
==Grid-Based Score== <br />
DOCK needs a fast scoring function to evaluate poses rapidly during growth. The energy grid is used for this. The grid stores the non-bonded Molecular Mechanics Potential of the receptor at each grid point. <br />
[[Image:Mm-equation.png|450px|center]]<br />
Grid can be called under descriptor score but it is suggested to not mix grid-based and cartesian space as that will dramatically increase computing time.<br />
===Grid Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
| grid_score_primary<br />
| Does the user want to perform grid-based energy scoring as the primary scoring function? || yes- <br />
|-<br />
| grid_score_rep_rad_scale<br />
| Scalar multiplier of the radii for the repulsive portion of the VDW energy component only when grid score is turned on || 1.0<br />
|-<br />
| grid_score_vdw_scale <br />
| Scalar multiplier of the VDW energy component || 1<br />
|-<br />
| grid_score_turn_off_vdw <br />
| A flag to turn off vdw portion of scoring function when grid score vdw scale = 0 || yes<br />
|-<br />
| grid_score_es_scale <br />
| Flag to scale up or down the es portion of the scoring function when es scale is turned on || 1<br />
|-<br />
| grid_score_turn_off_es <br />
| A flag to turn off es portion of scoring function when grid score es scale = 0 || yes<br />
|-<br />
| grid_score_grid_prefix <br />
| The prefix to the grid files containing the desired nrg/bmp grid || grid<br />
|-<br />
|}<br />
<br />
===Grid Score Output Components===<br />
These values will be printed in the header of the mol2 file post DOCK process.<br />
<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
| Grid_score<br />
| Sum of the VDW and ES interactions <br />
|-<br />
| Grid_vdw_energy<br />
| VDW interaction between the ligand grid<br />
|-<br />
| Grid_es_energy<br />
| ES interaction betweent eh ligand and grid<br />
|}<br />
<br />
== Continuous/DOCK Cartesian Energy Score==<br />
Continuous scoring may be used to evaluate a ligand:receptor complex without the investment of a grid calculation, or to perform a more detailed calculation without the numerical approximation of the grid. Continuous score is implemented under Descriptor Score as well. Continuous score is a cartesian based score and can be combined with other Cartesian based scores with very little computational expense.<br />
<br />
===Continuous/DCE Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
|continuous_score_primary<br />
| Does the user want to perform continuous non-grid scoring as the primary scoring function?<br />
| no<br />
|-<br />
|continuous_score_secondary <br />
| Does the user want to perform continuous non-grid scoring as the secondary scoring function? <br />
|no<br />
|-<br />
|cont_score_rec_filename <br />
|File that contains receptor coordinates <br />
|receptor.mol2<br />
|-<br />
|cont_score_att_exp <br />
|VDW Lennard-Jones potential attractive exponent <br />
|6<br />
|-<br />
|cont_score_rep_exp <br />
|VDW Lennard-Jones potential repulsive exponent <br />
|12<br />
|-<br />
|cont_score_rep_rad_scale <br />
|Scalar multiplier of the radii for the repulsive portion of the vdw energy component only <br />
|1.0<br />
|-<br />
|cont_score_use_dist_dep_dielectric <br />
|Distance dependent dielectric switch <br />
|yes<br />
|-<br />
|cont_score_dielectric <br />
|Dielectric constant for the electrostatic term <br />
|<br />
|- <br />
|cont_score_vdw_scale <br />
|Scalar multiplier of vdw energy component <br />
|1 <br />
|-<br />
|cont_score_vdw_scale <br />
|Flag to turn off vdw portion of the scoring function when cont_score_vdw_scale=0 <br />
|yes<br />
|- <br />
|cont_score_es_scale <br />
|Scalar multiplier of electrostatic energy component <br />
|1.0 <br />
|-<br />
|cont_score_turn_off_es <br />
|Flag to turn off es portion of the scoring function when cont_score_es_scale = 0 <br />
|yes<br />
|-<br />
|}<br />
<br />
===Continuous/DCE Score Output Components===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
|Continuous-score<br />
|sum of the van der Waals and electrostatic interactions<br />
|-<br />
|Continuous_vdw_energy<br />
|VDW interaction between ligand and receptor<br />
|-<br />
|Continuous_es_energy<br />
|ES interaction between the ligand and receptor<br />
|-<br />
|}<br />
<br />
==Footprint Similarity Score==<br />
The Footprint Similarity Score is a scoring function that calculates intermolecular hydrogen bonds and footprint comparisons, in addition to standard intermolecular energies (VDW and ES). <br />
<br />
Intermolecular Energies (VDW, ES) are calculated the same way as in Continuous Score.<br />
<br />
A geometric definition of Hydrogen bonds is employed. We define 3 atoms XD, HD, and XA as the heavy atom donor, donated hydrogen, and heavy atom acceptor, respectively. There is a hydrogen bond present if the following two conditions are met:<br />
<br />
# The distance between HD and XA is less than or equal to 2.5 angstroms;<br />
# The angle defined by XD, HD, and XA is between 120 and 180 degrees.<br />
<br />
Footprints are a per-residue decomposition of interactions between the ligand and the receptor. This can be performed for all three terms VDW, ES, HB.</div>Lprentishttps://ringo.ams.stonybrook.edu/index.php?title=Scoring_Functions&diff=13079Scoring Functions2020-04-14T17:53:06Z<p>Lprentis: </p>
<hr />
<div>DOCK uses several types of scoring functions to discriminate among orientations and molecules. Scoring is requested using the score_molecules parameter. A large portion of scoring functions can be called through descriptor score (but not all). Those with descriptor score functionality will be denoted as such. <br />
<br />
==Grid-Based Score== <br />
DOCK needs a fast scoring function to evaluate poses rapidly during growth. The energy grid is used for this. The grid stores the non-bonded Molecular Mechanics Potential of the receptor at each grid point. <br />
[[Image:Mm-equation.png|450px|center]]<br />
Grid can be called under descriptor score but it is suggested to not mix grid-based and cartesian space as that will dramatically increase computing time.<br />
===Grid Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
| grid_score_primary<br />
| Does the user want to perform grid-based energy scoring as the primary scoring function? || yes- <br />
|-<br />
| grid_score_rep_rad_scale<br />
| Scalar multiplier of the radii for the repulsive portion of the VDW energy component only when grid score is turned on || 1.0<br />
|-<br />
| grid_score_vdw_scale <br />
| Scalar multiplier of the VDW energy component || 1<br />
|-<br />
| grid_score_turn_off_vdw <br />
| A flag to turn off vdw portion of scoring function when grid score vdw scale = 0 || yes<br />
|-<br />
| grid_score_es_scale <br />
| Flag to scale up or down the es portion of the scoring function when es scale is turned on || 1<br />
|-<br />
| grid_score_turn_off_es <br />
| A flag to turn off es portion of scoring function when grid score es scale = 0 || yes<br />
|-<br />
| grid_score_grid_prefix <br />
| The prefix to the grid files containing the desired nrg/bmp grid || grid<br />
|-<br />
|}<br />
<br />
===Grid Score Output Components===<br />
These values will be printed in the header of the mol2 file post DOCK process.<br />
<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
| Grid_score<br />
| Sum of the VDW and ES interactions <br />
|-<br />
| Grid_vdw_energy<br />
| VDW interaction between the ligand grid<br />
|-<br />
| Grid_es_energy<br />
| ES interaction betweent eh ligand and grid<br />
|}<br />
<br />
== Continuous/DOCK Cartesian Energy Score==<br />
Continuous scoring may be used to evaluate a ligand:receptor complex without the investment of a grid calculation, or to perform a more detailed calculation without the numerical approximation of the grid. Continuous score is implemented under Descriptor Score as well. Continuous score is a cartesian based score and can be combined with other Cartesian based scores with very little computational expense.<br />
<br />
===Continuous/DCE Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
|continuous_score_primary<br />
| Does the user want to perform continuous non-grid scoring as the primary scoring function?<br />
| no<br />
|-<br />
|continuous_score_secondary <br />
| Does the user want to perform continuous non-grid scoring as the secondary scoring function? <br />
|no<br />
|-<br />
|cont_score_rec_filename <br />
|File that contains receptor coordinates <br />
|receptor.mol2<br />
|-<br />
|cont_score_att_exp <br />
|VDW Lennard-Jones potential attractive exponent <br />
|6<br />
|-<br />
|cont_score_rep_exp <br />
|VDW Lennard-Jones potential repulsive exponent <br />
|12<br />
|-<br />
|cont_score_rep_rad_scale <br />
|Scalar multiplier of the radii for the repulsive portion of the vdw energy component only <br />
|1.0<br />
|-<br />
|cont_score_use_dist_dep_dielectric <br />
|Distance dependent dielectric switch <br />
|yes<br />
|-<br />
|cont_score_dielectric <br />
|Dielectric constant for the electrostatic term <br />
|<br />
|- <br />
|cont_score_vdw_scale <br />
|Scalar multiplier of vdw energy component <br />
|1 <br />
|-<br />
|cont_score_vdw_scale <br />
|Flag to turn off vdw portion of the scoring function when cont_score_vdw_scale=0 <br />
|yes<br />
|- <br />
|cont_score_es_scale <br />
|Scalar multiplier of electrostatic energy component <br />
|1.0 <br />
|-<br />
|cont_score_turn_off_es <br />
|Flag to turn off es portion of the scoring function when cont_score_es_scale = 0 <br />
|yes<br />
|-<br />
|}<br />
<br />
===Continuous/DCE Score Output Components===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
|Continuous-score<br />
|sum of the van der Waals and electrostatic interactions<br />
|-<br />
|Continuous_vdw_energy<br />
|VDW interaction between ligand and receptor<br />
|-<br />
|Continuous_es_energy<br />
|ES interaction between the ligand and receptor<br />
|-<br />
|}<br />
<br />
==Footprint Similarity Score==<br />
The Footprint Similarity Score is a scoring function that calculates intermolecular hydrogen bonds and footprint comparisons, in addition to standard intermolecular energies (VDW and ES). <br />
<br />
Intermolecular Energies (VDW, ES) are calculated the same way as in Continuous Score.<br />
<br />
A geometric definition of Hydrogen bonds is employed. We define 3 atoms XD, HD, and XA as the heavy atom donor, donated hydrogen, and heavy atom acceptor, respectively. There is a hydrogen bond present if the following two conditions are met:<br />
<br />
# The distance between HD and XA is less than or equal to 2.5 angstroms;<br />
<br />
# The angle defined by XD, HD, and XA is between 120 and 180 degrees.<br />
<br />
Footprints are a per-residue decomposition of interactions between the ligand and the receptor. This can be performed for all three terms VDW, ES, HB.</div>Lprentishttps://ringo.ams.stonybrook.edu/index.php?title=Scoring_Functions&diff=13078Scoring Functions2020-04-14T17:50:39Z<p>Lprentis: /* Continuous Score/DOCK Cartesian Energy */</p>
<hr />
<div>DOCK uses several types of scoring functions to discriminate among orientations and molecules. Scoring is requested using the score_molecules parameter. A large portion of scoring functions can be called through descriptor score (but not all). Those with descriptor score functionality will be denoted as such. <br />
<br />
==Grid-Based Score== <br />
DOCK needs a fast scoring function to evaluate poses rapidly during growth. The energy grid is used for this. The grid stores the non-bonded Molecular Mechanics Potential of the receptor at each grid point. <br />
[[Image:Mm-equation.png|450px|center]]<br />
Grid can be called under descriptor score but it is suggested to not mix grid-based and cartesian space as that will dramatically increase computing time.<br />
===Grid Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
| grid_score_primary<br />
| Does the user want to perform grid-based energy scoring as the primary scoring function? || yes- <br />
|-<br />
| grid_score_rep_rad_scale<br />
| Scalar multiplier of the radii for the repulsive portion of the VDW energy component only when grid score is turned on || 1.0<br />
|-<br />
| grid_score_vdw_scale <br />
| Scalar multiplier of the VDW energy component || 1<br />
|-<br />
| grid_score_turn_off_vdw <br />
| A flag to turn off vdw portion of scoring function when grid score vdw scale = 0 || yes<br />
|-<br />
| grid_score_es_scale <br />
| Flag to scale up or down the es portion of the scoring function when es scale is turned on || 1<br />
|-<br />
| grid_score_turn_off_es <br />
| A flag to turn off es portion of scoring function when grid score es scale = 0 || yes<br />
|-<br />
| grid_score_grid_prefix <br />
| The prefix to the grid files containing the desired nrg/bmp grid || grid<br />
|-<br />
|}<br />
<br />
===Grid Score Output Components===<br />
These values will be printed in the header of the mol2 file post DOCK process.<br />
<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
| Grid_score<br />
| Sum of the VDW and ES interactions <br />
|-<br />
| Grid_vdw_energy<br />
| VDW interaction between the ligand grid<br />
|-<br />
| Grid_es_energy<br />
| ES interaction betweent eh ligand and grid<br />
|}<br />
<br />
== Continuous/DOCK Cartesian Energy Score==<br />
Continuous scoring may be used to evaluate a ligand:receptor complex without the investment of a grid calculation, or to perform a more detailed calculation without the numerical approximation of the grid. Continuous score is implemented under Descriptor Score as well. Continuous score is a cartesian based score and can be combined with other Cartesian based scores with very little computational expense.<br />
<br />
===Continuous/DCE Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
|continuous_score_primary<br />
| Does the user want to perform continuous non-grid scoring as the primary scoring function?<br />
| no<br />
|-<br />
|continuous_score_secondary <br />
| Does the user want to perform continuous non-grid scoring as the secondary scoring function? <br />
|no<br />
|-<br />
|cont_score_rec_filename <br />
|File that contains receptor coordinates <br />
|receptor.mol2<br />
|-<br />
|cont_score_att_exp <br />
|VDW Lennard-Jones potential attractive exponent <br />
|6<br />
|-<br />
|cont_score_rep_exp <br />
|VDW Lennard-Jones potential repulsive exponent <br />
|12<br />
|-<br />
|cont_score_rep_rad_scale <br />
|Scalar multiplier of the radii for the repulsive portion of the vdw energy component only <br />
|1.0<br />
|-<br />
|cont_score_use_dist_dep_dielectric <br />
|Distance dependent dielectric switch <br />
|yes<br />
|-<br />
|cont_score_dielectric <br />
|Dielectric constant for the electrostatic term <br />
|<br />
|- <br />
|cont_score_vdw_scale <br />
|Scalar multiplier of vdw energy component <br />
|1 <br />
|-<br />
|cont_score_vdw_scale <br />
|Flag to turn off vdw portion of the scoring function when cont_score_vdw_scale=0 <br />
|yes<br />
|- <br />
|cont_score_es_scale <br />
|Scalar multiplier of electrostatic energy component <br />
|1.0 <br />
|-<br />
|cont_score_turn_off_es <br />
|Flag to turn off es portion of the scoring function when cont_score_es_scale = 0 <br />
|yes<br />
|-<br />
|}<br />
<br />
===Continuous/DCE Score Output Components===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
|Continuous-score<br />
|sum of the van der Waals and electrostatic interactions<br />
|-<br />
|Continuous_vdw_energy<br />
|VDW interaction between ligand and receptor<br />
|-<br />
|Continuous_es_energy<br />
|ES interaction between the ligand and receptor<br />
|-<br />
|}</div>Lprentishttps://ringo.ams.stonybrook.edu/index.php?title=Scoring_Functions&diff=13077Scoring Functions2020-04-14T17:50:14Z<p>Lprentis: /* Continuous/DCE Score Output Components */</p>
<hr />
<div>DOCK uses several types of scoring functions to discriminate among orientations and molecules. Scoring is requested using the score_molecules parameter. A large portion of scoring functions can be called through descriptor score (but not all). Those with descriptor score functionality will be denoted as such. <br />
<br />
==Grid-Based Score== <br />
DOCK needs a fast scoring function to evaluate poses rapidly during growth. The energy grid is used for this. The grid stores the non-bonded Molecular Mechanics Potential of the receptor at each grid point. <br />
[[Image:Mm-equation.png|450px|center]]<br />
Grid can be called under descriptor score but it is suggested to not mix grid-based and cartesian space as that will dramatically increase computing time.<br />
===Grid Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
| grid_score_primary<br />
| Does the user want to perform grid-based energy scoring as the primary scoring function? || yes- <br />
|-<br />
| grid_score_rep_rad_scale<br />
| Scalar multiplier of the radii for the repulsive portion of the VDW energy component only when grid score is turned on || 1.0<br />
|-<br />
| grid_score_vdw_scale <br />
| Scalar multiplier of the VDW energy component || 1<br />
|-<br />
| grid_score_turn_off_vdw <br />
| A flag to turn off vdw portion of scoring function when grid score vdw scale = 0 || yes<br />
|-<br />
| grid_score_es_scale <br />
| Flag to scale up or down the es portion of the scoring function when es scale is turned on || 1<br />
|-<br />
| grid_score_turn_off_es <br />
| A flag to turn off es portion of scoring function when grid score es scale = 0 || yes<br />
|-<br />
| grid_score_grid_prefix <br />
| The prefix to the grid files containing the desired nrg/bmp grid || grid<br />
|-<br />
|}<br />
<br />
===Grid Score Output Components===<br />
These values will be printed in the header of the mol2 file post DOCK process.<br />
<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
| Grid_score<br />
| Sum of the VDW and ES interactions <br />
|-<br />
| Grid_vdw_energy<br />
| VDW interaction between the ligand grid<br />
|-<br />
| Grid_es_energy<br />
| ES interaction betweent eh ligand and grid<br />
|}<br />
<br />
== Continuous Score/DOCK Cartesian Energy ==<br />
Continuous scoring may be used to evaluate a ligand:receptor complex without the investment of a grid calculation, or to perform a more detailed calculation without the numerical approximation of the grid. Continuous score is implemented under Descriptor Score as well. Continuous score is a cartesian based score and can be combined with other Cartesian based scores with very little computational expense.<br />
<br />
===Continuous/DCE Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
|continuous_score_primary<br />
| Does the user want to perform continuous non-grid scoring as the primary scoring function?<br />
| no<br />
|-<br />
|continuous_score_secondary <br />
| Does the user want to perform continuous non-grid scoring as the secondary scoring function? <br />
|no<br />
|-<br />
|cont_score_rec_filename <br />
|File that contains receptor coordinates <br />
|receptor.mol2<br />
|-<br />
|cont_score_att_exp <br />
|VDW Lennard-Jones potential attractive exponent <br />
|6<br />
|-<br />
|cont_score_rep_exp <br />
|VDW Lennard-Jones potential repulsive exponent <br />
|12<br />
|-<br />
|cont_score_rep_rad_scale <br />
|Scalar multiplier of the radii for the repulsive portion of the vdw energy component only <br />
|1.0<br />
|-<br />
|cont_score_use_dist_dep_dielectric <br />
|Distance dependent dielectric switch <br />
|yes<br />
|-<br />
|cont_score_dielectric <br />
|Dielectric constant for the electrostatic term <br />
|<br />
|- <br />
|cont_score_vdw_scale <br />
|Scalar multiplier of vdw energy component <br />
|1 <br />
|-<br />
|cont_score_vdw_scale <br />
|Flag to turn off vdw portion of the scoring function when cont_score_vdw_scale=0 <br />
|yes<br />
|- <br />
|cont_score_es_scale <br />
|Scalar multiplier of electrostatic energy component <br />
|1.0 <br />
|-<br />
|cont_score_turn_off_es <br />
|Flag to turn off es portion of the scoring function when cont_score_es_scale = 0 <br />
|yes<br />
|-<br />
|}<br />
<br />
===Continuous/DCE Score Output Components===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
|Continuous-score<br />
|sum of the van der Waals and electrostatic interactions<br />
|-<br />
|Continuous_vdw_energy<br />
|VDW interaction between ligand and receptor<br />
|-<br />
|Continuous_es_energy<br />
|ES interaction between the ligand and receptor<br />
|-<br />
|}</div>Lprentishttps://ringo.ams.stonybrook.edu/index.php?title=Scoring_Functions&diff=13076Scoring Functions2020-04-14T17:48:49Z<p>Lprentis: /* Continuous Score/DOCK Cartesian Energy */</p>
<hr />
<div>DOCK uses several types of scoring functions to discriminate among orientations and molecules. Scoring is requested using the score_molecules parameter. A large portion of scoring functions can be called through descriptor score (but not all). Those with descriptor score functionality will be denoted as such. <br />
<br />
==Grid-Based Score== <br />
DOCK needs a fast scoring function to evaluate poses rapidly during growth. The energy grid is used for this. The grid stores the non-bonded Molecular Mechanics Potential of the receptor at each grid point. <br />
[[Image:Mm-equation.png|450px|center]]<br />
Grid can be called under descriptor score but it is suggested to not mix grid-based and cartesian space as that will dramatically increase computing time.<br />
===Grid Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
| grid_score_primary<br />
| Does the user want to perform grid-based energy scoring as the primary scoring function? || yes- <br />
|-<br />
| grid_score_rep_rad_scale<br />
| Scalar multiplier of the radii for the repulsive portion of the VDW energy component only when grid score is turned on || 1.0<br />
|-<br />
| grid_score_vdw_scale <br />
| Scalar multiplier of the VDW energy component || 1<br />
|-<br />
| grid_score_turn_off_vdw <br />
| A flag to turn off vdw portion of scoring function when grid score vdw scale = 0 || yes<br />
|-<br />
| grid_score_es_scale <br />
| Flag to scale up or down the es portion of the scoring function when es scale is turned on || 1<br />
|-<br />
| grid_score_turn_off_es <br />
| A flag to turn off es portion of scoring function when grid score es scale = 0 || yes<br />
|-<br />
| grid_score_grid_prefix <br />
| The prefix to the grid files containing the desired nrg/bmp grid || grid<br />
|-<br />
|}<br />
<br />
===Grid Score Output Components===<br />
These values will be printed in the header of the mol2 file post DOCK process.<br />
<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
| Grid_score<br />
| Sum of the VDW and ES interactions <br />
|-<br />
| Grid_vdw_energy<br />
| VDW interaction between the ligand grid<br />
|-<br />
| Grid_es_energy<br />
| ES interaction betweent eh ligand and grid<br />
|}<br />
<br />
== Continuous Score/DOCK Cartesian Energy ==<br />
Continuous scoring may be used to evaluate a ligand:receptor complex without the investment of a grid calculation, or to perform a more detailed calculation without the numerical approximation of the grid. Continuous score is implemented under Descriptor Score as well. Continuous score is a cartesian based score and can be combined with other Cartesian based scores with very little computational expense.<br />
<br />
===Continuous/DCE Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
|continuous_score_primary<br />
| Does the user want to perform continuous non-grid scoring as the primary scoring function?<br />
| no<br />
|-<br />
|continuous_score_secondary <br />
| Does the user want to perform continuous non-grid scoring as the secondary scoring function? <br />
|no<br />
|-<br />
|cont_score_rec_filename <br />
|File that contains receptor coordinates <br />
|receptor.mol2<br />
|-<br />
|cont_score_att_exp <br />
|VDW Lennard-Jones potential attractive exponent <br />
|6<br />
|-<br />
|cont_score_rep_exp <br />
|VDW Lennard-Jones potential repulsive exponent <br />
|12<br />
|-<br />
|cont_score_rep_rad_scale <br />
|Scalar multiplier of the radii for the repulsive portion of the vdw energy component only <br />
|1.0<br />
|-<br />
|cont_score_use_dist_dep_dielectric <br />
|Distance dependent dielectric switch <br />
|yes<br />
|-<br />
|cont_score_dielectric <br />
|Dielectric constant for the electrostatic term <br />
|<br />
|- <br />
|cont_score_vdw_scale <br />
|Scalar multiplier of vdw energy component <br />
|1 <br />
|-<br />
|cont_score_vdw_scale <br />
|Flag to turn off vdw portion of the scoring function when cont_score_vdw_scale=0 <br />
|yes<br />
|- <br />
|cont_score_es_scale <br />
|Scalar multiplier of electrostatic energy component <br />
|1.0 <br />
|-<br />
|cont_score_turn_off_es <br />
|Flag to turn off es portion of the scoring function when cont_score_es_scale = 0 <br />
|yes<br />
|-<br />
|}<br />
<br />
===Continuous/DCE Score Output Components===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
|}</div>Lprentishttps://ringo.ams.stonybrook.edu/index.php?title=Scoring_Functions&diff=13075Scoring Functions2020-04-14T17:47:36Z<p>Lprentis: /* Continuous/DCE Score Parameters */</p>
<hr />
<div>DOCK uses several types of scoring functions to discriminate among orientations and molecules. Scoring is requested using the score_molecules parameter. A large portion of scoring functions can be called through descriptor score (but not all). Those with descriptor score functionality will be denoted as such. <br />
<br />
==Grid-Based Score== <br />
DOCK needs a fast scoring function to evaluate poses rapidly during growth. The energy grid is used for this. The grid stores the non-bonded Molecular Mechanics Potential of the receptor at each grid point. <br />
[[Image:Mm-equation.png|450px|center]]<br />
Grid can be called under descriptor score but it is suggested to not mix grid-based and cartesian space as that will dramatically increase computing time.<br />
===Grid Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
| grid_score_primary<br />
| Does the user want to perform grid-based energy scoring as the primary scoring function? || yes- <br />
|-<br />
| grid_score_rep_rad_scale<br />
| Scalar multiplier of the radii for the repulsive portion of the VDW energy component only when grid score is turned on || 1.0<br />
|-<br />
| grid_score_vdw_scale <br />
| Scalar multiplier of the VDW energy component || 1<br />
|-<br />
| grid_score_turn_off_vdw <br />
| A flag to turn off vdw portion of scoring function when grid score vdw scale = 0 || yes<br />
|-<br />
| grid_score_es_scale <br />
| Flag to scale up or down the es portion of the scoring function when es scale is turned on || 1<br />
|-<br />
| grid_score_turn_off_es <br />
| A flag to turn off es portion of scoring function when grid score es scale = 0 || yes<br />
|-<br />
| grid_score_grid_prefix <br />
| The prefix to the grid files containing the desired nrg/bmp grid || grid<br />
|-<br />
|}<br />
<br />
===Grid Score Output Components===<br />
These values will be printed in the header of the mol2 file post DOCK process.<br />
<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Output Component<br />
! Description<br />
|-<br />
| Grid_score<br />
| Sum of the VDW and ES interactions <br />
|-<br />
| Grid_vdw_energy<br />
| VDW interaction between the ligand grid<br />
|-<br />
| Grid_es_energy<br />
| ES interaction betweent eh ligand and grid<br />
|}<br />
<br />
== Continuous Score/DOCK Cartesian Energy ==<br />
Continuous scoring may be used to evaluate a ligand:receptor complex without the investment of a grid calculation, or to perform a more detailed calculation without the numerical approximation of the grid. Continuous score is implemented under Descriptor Score as well. Continuous score is a cartesian based score and can be combined with other Cartesian based scores with very little computational expense.<br />
<br />
===Continuous/DCE Score Parameters===<br />
{| class="wikitable" <br />
|+ <br />
|-<br />
! Parameter<br />
! Description<br />
! Default Value<br />
|-<br />
|continuous_score_primary<br />
| Does the user want to perform continuous non-grid scoring as the primary scoring function?<br />
| no<br />
|-<br />
|continuous_score_secondary <br />
| Does the user want to perform continuous non-grid scoring as the secondary scoring function? <br />
|no<br />
|-<br />
|cont_score_rec_filename <br />
|File that contains receptor coordinates <br />
|receptor.mol2<br />
|-<br />
|cont_score_att_exp <br />
|VDW Lennard-Jones potential attractive exponent <br />
|6<br />
|-<br />
|cont_score_rep_exp <br />
|VDW Lennard-Jones potential repulsive exponent <br />
|12<br />
|-<br />
|cont_score_rep_rad_scale <br />
|Scalar multiplier of the radii for the repulsive portion of the vdw energy component only <br />
|1.0<br />
|-<br />
|cont_score_use_dist_dep_dielectric <br />
|Distance dependent dielectric switch <br />
|yes<br />
|-<br />
|cont_score_dielectric <br />
|Dielectric constant for the electrostatic term <br />
|<br />
|- <br />
|cont_score_vdw_scale <br />
|Scalar multiplier of vdw energy component <br />
|1 <br />
|-<br />
|cont_score_vdw_scale <br />
|Flag to turn off vdw portion of the scoring function when cont_score_vdw_scale=0 <br />
|yes<br />
|- <br />
|cont_score_es_scale <br />
|Scalar multiplier of electrostatic energy component <br />
|1.0 <br />
|-<br />
|cont_score_turn_off_es <br />
|Flag to turn off es portion of the scoring function when cont_score_es_scale = 0 <br />
|yes<br />
|-<br />
|}</div>Lprentis