View source for 2019 DOCK GA tutorial 1 with 2NNQ

For this experiment required files will include
2NNQ.lig.mol2.
Make sure that you use a charged ligand with hydrogens
[[File:2NNQ_lig_wH_charged.PNG|thumb|Ligand with hydrogens and charged]]
=='''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 (Using the paths to your compilation of DOCK in place of ${DOCK_DIR})
     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                                                ${DOCK_DIR}/parameters/vdw_AMBER_parm99.defn 
     flex_defn_file                                               ${DOCK_DIR}/parameters/flex.defn
     flex_drive_file                                              ${DOCK_DIR}/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 
     python ${DOCK_DIR}/bin/combine_torenv.py 2NNQ.fraglib_torenv.dat ${DOCK_DIR}/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

For the last step send this to the slurm servers generate the results. This test will occur for 500 generations and is too computationally intensive for the head node.

First create a new file to send to the slurm system
      vim 2NNQ_GA.sh
Following this input the following into the 2NNQ_GA.sh script
      #!/bin/bash
      #SBATCH --time=48:00:00
      #SBATCH --nodes=1
      #SBATCH --ntasks=40
      #SBATCH --job-name=2NNQ_GA_input
      #SBATCH --output=2NNQ_GA_output
      #SBATCH -p long-40core

      cd $SLURM_SUBMIT_DIR
      dock6 -i 2NNQ_GA.in -o 2NNQ_GA.out
Following this you will send the script
      qsub 2NNQ_GA.sh

To check on its status use the following
      qstat -u username