Development Goals Archive

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

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