2022 Denovo tutorial 3 with PDBID 1X70
From Rizzo_Lab
System Preparation
Directory Setup
ATTENTION: This tutorial requires you to have first completed the 2022 1X70 VS tutorial: https://ringo.ams.stonybrook.edu/index.php/2022_DOCK_tutorial_3_with_PDBID_1X70
Make a new directory:
mkdir 09.focus_dn
Now inside 09.focus_dn, make the following DOCK6 input file: "fraglib.in"
conformer_search_type flex write_fragment_libraries yes fragment_library_prefix fraglib fragment_library_freq_cutoff 1 fragment_library_sort_method freq fragment_library_trans_origin no use_internal_energy yes internal_energy_rep_exp 12 internal_energy_cutoff 100.0 ligand_atom_file ../01.structures/715.mol2 limit_max_ligands no skip_molecule no read_mol_solvation no calculate_rmsd no use_database_filter no orient_ligand yes automated_matching yes receptor_site_file ../02.spheres/selected_spheres.sph max_orientations 1000 critical_points no chemical_matching no use_ligand_spheres no bump_filter no score_molecules no atom_model all vdw_defn_file /gpfs/projects/AMS536/zzz.programs/dock6.9_release/parameters/vdw_AMBER_parm99.defn flex_defn_file /gpfs/projects/AMS536/zzz.programs/dock6.9_release/parameters/flex.defn flex_drive_file /gpfs/projects/AMS536/zzz.programs/dock6.9_release/parameters/flex_drive.tbl ligand_outfile_prefix fragment.out write_orientations no num_scored_conformers 1 rank_ligands no
dock6 -i fraglib.in -o fraglib.out
You should end up with 5 different files:
"fraglib_rigid.mol2 fraglib_scaffold.mol2 fraglib_sidechain.mol2 fraglib_torenv.dat fraglib_linker.mol2"
Each file contains fragments defined by the number of places they were cut at during fragment generation.
Now load up Chimera:
Tools > Binding/Surface Analysis > View Dock > Load fraglib_linker.mol2
Load fraglib_sidechain.mol2
Load both
Focused Growth
Make the following dock6 input file: "focus.in"
conformer_search_type denovo dn_fraglib_scaffold_file fraglib_scaffold.mol2 dn_fraglib_linker_file fraglib_linker.mol2 dn_fraglib_sidechain_file fraglib_sidechain.mol2 dn_user_specified_anchor no dn_use_torenv_table yes dn_torenv_table fraglib_torenv.dat dn_sampling_method graph dn_graph_max_picks 30 dn_graph_breadth 3 dn_graph_depth 2 dn_graph_temperature 100.0 dn_pruning_conformer_score_cutoff 100.0 dn_pruning_conformer_score_scaling_factor 1.0 dn_pruning_clustering_cutoff 100.0 dn_constraint_mol_wt 550.0 dn_constraint_rot_bon 15 dn_constraint_formal_charge 2.0 dn_heur_unmatched_num 1 dn_heur_matched_rmsd 2.0 dn_unique_anchors 4 dn_max_grow_layers 9 dn_max_root_size 25 dn_max_layer_size 25 dn_max_current_aps 5 dn_max_scaffolds_per_layer 1 dn_write_checkpoints yes dn_write_prune_dump no dn_write_orients yes dn_write_growth_trees yes dn_output_prefix dn_focus.out use_internal_energy yes internal_energy_rep_exp 12 internal_energy_cutoff 100.0 use_database_filter no orient_ligand yes automated_matching yes receptor_site_file ../02.spheres/selected_spheres.sph max_orientations 1000 critical_points no chemical_matching no use_ligand_spheres 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 ../03.grid/grid multigrid_score_secondary no dock3.5_score_secondary no continuous_score_secondary no footprint_similarity_score_secondary no pharmacophore_score_secondary no descriptor_score_secondary no gbsa_zou_score_secondary no gbsa_hawkins_score_secondary no SASA_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 simplex_restraint_min no atom_model all vdw_defn_file /gpfs/projects/AMS536/zzz.programs/dock6.9_release/parameters/vdw_AMBER_parm99.defn flex_defn_file /gpfs/projects/AMS536/zzz.programs/dock6.9_release/parameters/vdw_de_novo.defn flex_drive_file /gpfs/projects/AMS536/zzz.programs/dock6.9_release/parameters/flex_drive.tbl
dock6 -i focus.in -o focus.out
You should get the following file: "dn_focus.out.denovo_build.mol2"
Load it in Chimera using viewdock, then load in the refence ligand
Tools > general controls > model panel > set the reference ligand to inactive and then move the fragments so they are not overlayed
