Difference between revisions of "Development Goals Archive"

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(→‎DOCK_DN - De Novo Design)
(→‎DOCK_GA - Genetic Algorithm)
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=DOCK_GA - Genetic Algorithm=
 
=DOCK_GA - Genetic Algorithm=
 +
=DOCK_GA - Genetic Algorithm=
 +
{| border="1" cellpadding="8" cellspacing="0" style="background:white; text-align:left; width:90%"
 +
|- style="background:lightblue"
 +
! style="width:50%" !|Tasks
 +
! style="width:10%" !|Owner
 +
! style="width:30%" !|Complete?
 +
|-
 +
|Horizontal pruning issue not catching chemically identical molecules || LEP || no
 +
|-
 +
|Fix bug that collapsed atom coordinates  || everywhere? nowhere? somewhere. || LEP || YES MUAHAHAHAHA!
 +
|-
 +
|Added Delimeter header ||conf_gen_ga || LEP || Yes
 +
|-
 +
|Fix xover only feature ||conf_gen_ga || LEP || Yes
 +
|-
 +
|Put in error messages for mut_rate > 1 || conf_gen_ga ||LEP || Yes
 +
|-
 +
|Manual user-defined mutation type ||conf_gen_ga || LEP || Yes
 +
|-
 +
|Remove check only option || conf_gen_ga || LEP || Yes
 +
|-
 +
|Add single molecule evolution in testcase in install dir. || install/test/genetic || LEP ||yes
 +
|-
 +
|Add leading 0's to xover output filenames || conf_gen_ga.cpp || JDB || no
 +
|-
 +
|DNM replacement unable to build list? || conf_gen_ga.cpp || JDB || no
 +
|-
 +
|Multi-layer replacement for Amides || conf_gen_ga.cpp || JDB || no
 +
|-
 +
|Compute delta slope of fitness score || congen_ga.cpp || BTB ||no
 +
|-
 +
| slow down molecular evolution so there are less drastic canges between each successive generation || congen_ga.cpp || BTB ||no
 +
|-
 +
| bring in new parents (e.g. from a pool of molecules) based on convergence || confgen_ga.cpp || BTB || no
 +
|-
 +
| user defined point vs on-the-fly convergence || confgen_ga.cpp || BTB || no
 +
|-
 +
| metropolis selection for tournament/roulette || conf_gen_ga.cpp || BTB  || no
 +
|-
 +
|}
 +
<br>
  
 +
 +
==To Do List==
 +
# tanimoto coefficient percent change - might be inaccurate due to tan coef behavior
 +
# Rotatable bond changes (???)
 +
# Limit number of aromatic rings.
 +
#-xover (guided based on score) - Good v Good ; Bad v Good ; Bad v Bad THIS
 +
#Nonexhaustive xover (pick subset of xover based on probability)
 +
#Nonexhaustive xover for each pair of parents - have a set number of bonds for xover rather than trying all of them.
 +
#Crossover on multiple points simultaneously (2-3 crossovers on a given pair to make 3+ children rather than 2+).
 +
#Adaptive maintenance of ensemble based on convergence (extinction, delta max, etc.).
 +
#Stop convergence.
 +
#Mutations-
 +
##Adaptive mutation rate - change rate of mutation based on some internal criteria.
 +
##Pick location of mutation based on some internal criteria.
 +
##Pick mutation type based on ensemble behavior.
 +
##If molecules are too large, boost deletion (useful for elitism).
 +
##If molecules are too small, boost additive mutations.
 +
##If molecules are too similar, boost replacements and substitutions.
 +
##mutation type selection based on probability vs ensemble
 +
##Complete x # y mutation so far so less prevalent etc
 +
##Note: 3 layer substitutions probably aren't going to work.
 +
##2-layer replacements.
 +
#fitness-
 +
##turn on and off niching adaptive/extinction
 +
##reduce boost of fragments and all poor mols with niching
 +
##pareto/mulitobjective ga
 +
#selection-
 +
##Adaptively keep differing #'s of parents and children based on some internal criteria (similarity?)
 +
#extinction-
 +
#which molecules are best-
 +
##best first pruning - now uses descriptor score even if niching ned to delta to fitness/niching when used
 +
## geometric diversity using Hingarian and Tan pruning
 +
#Determine whether the dummy vdw file is necessary for all DN (including GA) or just DN.
 +
#Choose crossover pairs based on measure of similarity (boost crossovers between dissimilar molecules).
 +
 +
== Known Bugs ==
 +
#Molecules Processed bug (dock.cpp)
 +
#verbose mol stats (amber typer)
 +
#molecule being renamed when going into repl even tho it's the same molecule
  
 
=DOCK_CV - Covalent Docking=
 
=DOCK_CV - Covalent Docking=

Revision as of 13:19, 24 October 2022

DOCK_VS - Virtual Screening/Traditional Docking

Tasks src Owner Complete?
verbose ==2 option in dock6 beta utils.cpp LEP yes
Add total conformers samples
Check amide bond rotation during sampling - it's nto a bug it was fixed back in 2014 LEP yes
Write out # of HBond Donors and Acceptors conf_gen_dn, library_file LEP yes
put in compiler directives to compile with or without timespec dock.cpp LEP yes
Fix bug that prints out 2/3 sigfigs instead of 6 for MW and FC library_file, filter, amber_typer LEP Yes
Fix nano/micro/milisecond timer dock.cpp GDRM Yes
ga flag and verbose == 2 for premin_mol in simplex simplex.cpp LEP Yes
Merge Hackathon changes to beta for clean faster code pow/memcpy/mpi pointers everywhere LEP Yes
Add Tip3p atom type to dock vdw.defn fingerprint LEP Yes
Hide secondary scoring function permanently lots LEP Yes
Merge GIST into latest dock grid, master_score, score_descriptor, score_gist LEP Yes
Add second layer of verbosity utils, conf_gen_dn so far LEP Yes
RDKit integration with DOCK GDM Yes
Modify Grid to show error on nonintegrality BTB Yes


DOCK_DN - De Novo Design

Task Owner Notes
Possible torenv check for dump molecules after capping before printing.
Overhaul the simple-build function Trent 6.10 release
When minimizing with descriptor score, make sure fingerprint is turned off xxx
Speed up fingerprint calculations by saving reference ligand as a permanent object WJA
Add pre-min conformations to growth trees WJA
Add verbose flag options WJA
Put molecular properties (RB, MW, etc) in mol2 header WJA
Put ensemble properties (RB, MW, etc) output stream at the end of each layer WJA
Check formal charge prune BCF
Combination of horizontal pruning metrics (let's consider dropping tanimoto prune and just using hungarian prune) WJA
Finish implementing growth trees WJA
Revisit orienting to make sure it is working as intended WJA
Fixed a bug where we were marking scaffold_this_layer as true for any fragment WJA
Update random sampling function to use last layer changes in graph function WJA
Do that same thing for the exhaustive function WJA
I don't think we ever clear the scaf_link_sid vector, we definitely should do that somewhere WJA
Update exhaustive to combine all frags into one library, just like graph / random. WJA
hbond accept/donor descriptor implementation Lauren
increase orienting verbose statistics for dn Chris
acceptance based on freq of torsenv John
secondary torenv check of prune dump molecules and testing Lauren & John
SMILEs and ZINC script (for dn and ga) Lauren & John
add dn name with date and counter function Lauren
Check MGS+(-50)TAN before and after fingerprinting fix for 663 systems Lauren
determine if random seed is reset for each aps Lauren
Create testset for each dn function Lauren
Test simple build function with merged de novo Lauren
clean make_unique script for release Lauren & Stephen
merge GA into dock/dn Lauren
MPI wrapper for 192 processors (8 nodes) for testsets on rizzo cluster Dwight & Lauren
Create short testsets for denovo frag gen, focused fragment generic for DOCK6.9 release Lauren
merge parameter files of de novo with DOCK Dwight & Lauren
add dn_defn file for separate defn with Hydrogens Lauren
Implement csingleton fix for orienting fragments with less than 3 heavy atoms Lauren
Test bfochtman fix for rotatable bonds within an user defined anchor Lauren
Test csingleton fix for orienting fragments with Du Lauren
Test MGS focused fragment library results with dn paper Lauren
editting script to calculate SMILE string of de novo molecules in OpenBabel Stephen
smooth function cutoff for mw Stephen
Rework VS protocol to integrate de novo protocol more smoothly Lauren & John
Fix torsion problem for prune_dump molecules Lauren & John

This is the Rizzo lab wiki page for coordinating bugs and progress on the de novo project.

Valgrind clean version of the code on cluster that Rizzo lab should be using:

Lauren: 

/gpfs/projects/rizzo/zzz.programs/dock6.9_release
This version includes all changes of the merge.

Path to Generic Fragment Library: 

/gpfs/projects/rizzo/leprentis/gen-frags-12

Path to Frequency Anchors: 

/gpfs/projects/rizzo/leprentis/zinc1_ancs_freq


List of SB2012 systems that we will use for tests:

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)

{5RB = 107; 6RB = 96; 7RB = 103; 8RB = 75; 9RB = 66; 10RB = 75; 11RB = 57; 12RB = 41; 13RB = 38; 14RB = 26; 15RB = 25} </br>

DOCK_GA - Genetic Algorithm

DOCK_GA - Genetic Algorithm

Tasks Owner Complete?
Horizontal pruning issue not catching chemically identical molecules LEP no
Fix bug that collapsed atom coordinates everywhere? nowhere? somewhere. LEP YES MUAHAHAHAHA!
Added Delimeter header conf_gen_ga LEP Yes
Fix xover only feature conf_gen_ga LEP Yes
Put in error messages for mut_rate > 1 conf_gen_ga LEP Yes
Manual user-defined mutation type conf_gen_ga LEP Yes
Remove check only option conf_gen_ga LEP Yes
Add single molecule evolution in testcase in install dir. install/test/genetic LEP yes
Add leading 0's to xover output filenames conf_gen_ga.cpp JDB no
DNM replacement unable to build list? conf_gen_ga.cpp JDB no
Multi-layer replacement for Amides conf_gen_ga.cpp JDB no
Compute delta slope of fitness score congen_ga.cpp BTB no
slow down molecular evolution so there are less drastic canges between each successive generation congen_ga.cpp BTB no
bring in new parents (e.g. from a pool of molecules) based on convergence confgen_ga.cpp BTB no
user defined point vs on-the-fly convergence confgen_ga.cpp BTB no
metropolis selection for tournament/roulette conf_gen_ga.cpp BTB no



To Do List

  1. tanimoto coefficient percent change - might be inaccurate due to tan coef behavior
  2. Rotatable bond changes (???)
  3. Limit number of aromatic rings.
  4. -xover (guided based on score) - Good v Good ; Bad v Good ; Bad v Bad THIS
  5. Nonexhaustive xover (pick subset of xover based on probability)
  6. Nonexhaustive xover for each pair of parents - have a set number of bonds for xover rather than trying all of them.
  7. Crossover on multiple points simultaneously (2-3 crossovers on a given pair to make 3+ children rather than 2+).
  8. Adaptive maintenance of ensemble based on convergence (extinction, delta max, etc.).
  9. Stop convergence.
  10. Mutations-
    1. Adaptive mutation rate - change rate of mutation based on some internal criteria.
    2. Pick location of mutation based on some internal criteria.
    3. Pick mutation type based on ensemble behavior.
    4. If molecules are too large, boost deletion (useful for elitism).
    5. If molecules are too small, boost additive mutations.
    6. If molecules are too similar, boost replacements and substitutions.
    7. mutation type selection based on probability vs ensemble
    8. Complete x # y mutation so far so less prevalent etc
    9. Note: 3 layer substitutions probably aren't going to work.
    10. 2-layer replacements.
  11. fitness-
    1. turn on and off niching adaptive/extinction
    2. reduce boost of fragments and all poor mols with niching
    3. pareto/mulitobjective ga
  12. selection-
    1. Adaptively keep differing #'s of parents and children based on some internal criteria (similarity?)
  13. extinction-
  14. which molecules are best-
    1. best first pruning - now uses descriptor score even if niching ned to delta to fitness/niching when used
    2. geometric diversity using Hingarian and Tan pruning
  15. Determine whether the dummy vdw file is necessary for all DN (including GA) or just DN.
  16. Choose crossover pairs based on measure of similarity (boost crossovers between dissimilar molecules).

Known Bugs

  1. Molecules Processed bug (dock.cpp)
  2. verbose mol stats (amber typer)
  3. molecule being renamed when going into repl even tho it's the same molecule

DOCK_CV - Covalent Docking

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