Testset Protocols
Contents
Rigid Docking Baseline Input
Ligand torsions are not sampled. The whole ligand is treated as the anchor and matched to the spheres. 0.3A grids are used with am1bcc charges on the ligand. amber99 charges and vdw parameters are used for everything else. If rank ligands are set to 'yes', dock does not report a cluster size. The number of simplex_max_iterations improves minimization while adding minimally to the runtime on the grid.
Fixed Anchor Docking Baseline
Anchor orientation is disabled. Instead, the ligand is minimized on the receptor coordinates (ligand.xtm.mol2). The largest anchor recovered is used for flexible growth. A clash overlap of 0.5 is used to avoid poor ligand conformations.
Flexible Docking Baseline
Flexible ligand docking where the largest anchor is oriented is matched to the spheres. Each anchor orient is grown along the torsions to generate poses.
On mathlab computers this binary is located at /home/sudipto/dock6/dock6_09-02-18/bin/dock6
Complete Input files for DOCK6 09-02-18
| Rigid Docking | Flexible Docking |
ligand_atom_file ligand.mol2 limit_max_ligands no skip_molecule no read_mol_solvation no calculate_rmsd yes use_rmsd_reference_mol no orient_ligand yes automated_matching yes receptor_site_file spheres.sph max_orientations 1000 critical_points no chemical_matching no use_ligand_spheres no use_internal_energy yes internal_energy_rep_exp 12 flexible_ligand no bump_filter no score_molecules yes contact_score_primary no contact_score_secondary no grid_score_primary yes grid_score_secondary no grid_score_rep_rad_scale 1 grid_score_vdw_scale 1 grid_score_es_scale 1 grid_score_grid_prefix grid dock3.5_score_secondary no continuous_score_secondary no gbsa_zou_score_secondary no gbsa_hawkins_score_secondary no amber_score_secondary no minimize_ligand yes simplex_max_iterations 1000 simplex_tors_premin_iterations 0 simplex_max_cycles 1 simplex_score_converge 0.1 simplex_cycle_converge 1.0 simplex_trans_step 1.0 simplex_rot_step 0.1 simplex_tors_step 10.0 simplex_random_seed 0 atom_model all vdw_defn_file vdw_AMBER_parm99.defn flex_defn_file flex.defn flex_drive_file flex_drive.tbl ligand_outfile_prefix rigid.dock2grid write_orientations no num_scored_conformers 5000 write_conformations no cluster_conformations yes cluster_rmsd_threshold 2.0 rank_ligands no |
ligand_atom_file ligand.mol2 limit_max_ligands no skip_molecule no read_mol_solvation no calculate_rmsd yes use_rmsd_reference_mol no orient_ligand yes automated_matching yes receptor_site_file spheres.sph max_orientations 1000 critical_points no chemical_matching no use_ligand_spheres no use_internal_energy yes internal_energy_rep_exp 12 flexible_ligand yes min_anchor_size 5 pruning_use_clustering yes pruning_max_orients 1000 pruning_clustering_cutoff 100 pruning_conformer_score_cutoff 100.0 use_clash_overlap no print_growth_tree no bump_filter no score_molecules yes contact_score_primary no contact_score_secondary no grid_score_primary yes grid_score_secondary no grid_score_rep_rad_scale 1 grid_score_vdw_scale 1 grid_score_es_scale 1 grid_score_grid_prefix grid dock3.5_score_secondary no continuous_score_secondary no gbsa_zou_score_secondary no gbsa_hawkins_score_secondary no amber_score_secondary 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 1.0 simplex_trans_step 1.0 simplex_rot_step 0.1 simplex_tors_step 10.0 simplex_anchor_max_iterations 500 simplex_grow_max_iterations 500 simplex_grow_tors_premin_iterations 0 simplex_random_seed 0 atom_model all vdw_defn_file vdw_AMBER_parm99.defn flex_defn_file flex.defn flex_drive_file flex_drive.tbl ligand_outfile_prefix flex.dock2grid write_orientations no num_scored_conformers 5000 write_conformations no cluster_conformations yes cluster_rmsd_threshold 2.0 rank_ligands no |
Minimizing on receptor coordinates
In order to remove any grid artifacts, you can minimize your ligand poses on the actual receptor coordinates. For this, set grid_score_primary=no, and select continuous_score as your primary scoring function. DOCK will ask you for a receptor mol2 file instead of a grid prefix. Do not use this for actual docking, as it will be very very slow. Instead, this is meant to rescore poses already generated by docking to the grid. You can also minimize the native ligand pose from the crystal structure to get a reference DOCK score.
Minimizing on the receptor coordinates may change your scores significantly in many cases, and when you are ranking several poses, might even change which pose is the top ranked pose.
