DOCK GA Tutorials
For this experiment required files will include 2NNQ.lig.mol2
I. Fragment Library Generation for 2NNQ
Fragment Libraries
For this experiment a general fragment library to account for all the possible ligands the GA can produce. A focused Fragment library will not be enough to account for all the possibilities since it is too small of a set of data.
The first step for this experiment is to generate a directory to perform the work in
mkdir 2NNQ_GA
Go into this new directory and then create another directory that will store all the fragment molecules
mkdir fraglib
Enter the file directory fraglib
cd fraglib
Create a new file called 2NNQ.fraglib
touch 2NNQ.fraglib
dock6 -i 2NNQ.fraglib
Answer the following prompts using these responses
conformer_search_type flex
write_fragment_libraries yes
fragment_library_prefix 2NNQ.fraglib
fragment_library_freq_cutoff 1
fragment_library_sort_method freq
fragment_library_trans_origin no
use_internal_energy no
ligand_atom_file ../../2NNQ_Tutorial/1.dockprep/2nnq_lig_withH.mol2
limit_max_ligands no
skip_molecule no
read_mol_solvation no
calculate_rmsd no
use_database_filter no
orient_ligand no
bump_filter no
score_molecules no
atom_model all
vdw_defn_file /gpfs/projects/AMS536/zzz.programs/dock6/parameters/vdw_AMBER_parm99.defn
flex_defn_file /gpfs/projects/AMS536/zzz.programs/dock6/parameters/flex.defn
flex_drive_file /gpfs/projects/AMS536/zzz.programs/dock6/parameters/flex_drive.tbl
ligand_outfile_prefix 2NNQ_frag_output
write_orientations no
num_scored_conformers 1
rank_ligands no
The only aspect that is relevant of this fragment library generated is the torsion environment that should be titled 2NNQ.fraglib_torenv.dat Following this step the torsion environments of this molecule will be combined with the file titled full_sorted_fraglib.dat using the python software combine_torenv.py
py /gpfs/projects/rizzo/zzz.programs/torsion_env_combination/combine_torenv.py 2NNQ.fraglib_torenv.dat /gpfs/projects/rizzo/zzz.programs/dock6.10_2019.06.18/parameters/fraglib_torenv.dat
This should generate a new list of torsion environments titled unique_full_sorted_fraglib.dat
II. Performing a GA using 2NNQ
For this part a new directory will be created in the 2NNQ_GA. This will just be 2NNQ_GA_results. cd into that directory and create a new file titled 2NNQ_GA.in.
mkdir 2NNQ_GA_results
cd 2NNQ_GA_results
touch 2NNQ_GA.in
Following this dock6 will be performed on the molecule
dock6 -i 2NNQ_GA.in -o 2NNQ_GA.out
Input the following in order to get the GA working properly. The file will ask for ga_mutations. This will prompt you with addition, deletion, substitution, and replacement mutations and respond yes to all them unless there is a specific purpose to your code to not include these mutation types.
conformer_search_type genetic
ga_molecule_file /Path/2nnq_lig_withH.mol2
ga_fraglib_scaffold_file /gpfs/projects/rizzo/zzz.programs/dock6.10_2019.06.14/parameters /fraglib_ga_scaffold.mol2
ga_fraglib_linker_file /gpfs/projects/rizzo/zzz.programs/dock6.10_2019.06.14/parameters /fraglib_linker.mol2
ga_fraglib_sidechain_file /gpfs/projects/rizzo/zzz.programs/dock6.10_2019.06.14/parameters/fraglib_sidechain.mol2
ga_torenv_table ../fraglib/unique_full_sorted_fraglib.dat
ga_max_generations 500
ga_xover_sampling_method_rand yes
ga_xover_max 150
ga_bond_tolerance 0.5
ga_angle_cutoff 0.14
ga_check_overlap no
ga_mutations yes
ga_mutate_addition yes
ga_mutate_deletion yes
ga_mutate_substitution yes
ga_mutate_replacement yes
ga_mutate_parents yes
ga_pmut_rate 0.3
ga_omut_rate 0.7
ga_max_mut_cycles 5
ga_mut_sampling_method rand
ga_num_random_picks 10
ga_max_root_size 5
ga_energy_cutoff 100
ga_heur_unmatched_num 2
ga_heur_matched_rmsd 2
ga_constraint_mol_wt 550
ga_constraint_rot_bon 10
ga_constraint_H_accept 10
ga_constraint_H_don 5
ga_constraint_formal_charge 4
ga_ensemble_size 200
ga_selection_method elitism
ga_elitism_combined no
ga_elitism_option max
ga_niching no
ga_selection_extinction no
ga_max_num_gen_with_no_crossover 1000
ga_output_prefix 2NNQ_GA_output
use_internal_energy yes
internal_energy_rep_exp 12
internal_energy_cutoff 100
use_database_filter no
orient_ligand no
bump_filter no
score_molecules yes
contact_score_primary no
grid_score_primary no
gist_score_primary no
multigrid_score_primary no
dock3.5_score_primary no
continuous_score_primary no
footprint_similarity_score_primary no
pharmacophore_score_primary no
hbond_score_primary no
descriptor_score_primary yes
descriptor_use_grid_score no
descriptor_use_multigrid_score no
descriptor_use_continuous_score no
descriptor_use_footprint_similarity no
descriptor_use_pharmacophore_score no
descriptor_use_tanimoto no
descriptor_use_hungarian no
descriptor_use_volume_overlap no
descriptor_use_gist no
minimize_ligand yes
minimize_anchor yes
minimize_flexible_growth yes
use_advanced_simplex_parameters no
simplex_max_cycles 1
simplex_score_converge 0.1
simplex_cycle_converge 1
simplex_trans_step 1
simplex_rot_step 0.1
simplex_tors_step 10
simplex_anchor_max_iterations 500
simplex_grow_max_iterations 500
simplex_grow_tors_premin_iterations 00
simplex_random_seed 0
simplex_restraint_min yes
simplex_coefficient_restraint 10
atom_model all
vdw_defn_file /gpfs/projects/AMS536/zzz.programs/dock6/parameters /vdw_AMBER_parm99.defn
flex_defn_file /gpfs/projects/AMS536/zzz.programs/dock6/parameters/flex.defn
flex_drive_file /gpfs/projects/AMS536/zzz.programs/dock6/parameters/flex_drive.tbl
