Difference between revisions of "2022 Denovo tutorial 1 with PDBID 6ME2"
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Stonybrook (talk | contribs) (→Focused de novo rescore) |
Stonybrook (talk | contribs) (→Focused de novo rescore) |
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num_scored_conformers 1 | num_scored_conformers 1 | ||
rank_ligands no | rank_ligands no | ||
| + | |||
| + | Once you have finished, vi into dn_rescore.sh and write the following to that file: | ||
| + | |||
| + | #!/bin/bash | ||
| + | #SBATCH --time=48:00:00 | ||
| + | #SBATCH --nodes=1 | ||
| + | #SBATCH --ntasks=28 | ||
| + | #SBATCH --job-name=dn_rescore | ||
| + | #SBATCH --output=dn_rescore.out | ||
| + | #SBATCH -p long-28core | ||
| + | |||
| + | cd $SLURM_SUBMIT_DIR | ||
| + | echo "starting Dock6.9 simulation" | ||
| + | /gpfs/projects/AMS536/zzz.programs/dock6.9_release/bin/dock6.mpi -i dn_rescore.in -o dn_rescore.out | ||
| + | |||
| + | To submit this job, type the following into the terminal: | ||
| + | |||
| + | dock6 -i rescore.in -o rescore.out | ||
| + | |||
| + | When this finishes, you will generate a couple of files, the most important of which is the descriptor.output_scored.mol2 file. Move that to the comupter you are using Chimera on and load that file into Chimera using ViewDock as described in the virtual screen tutorial. It is also a good idea to load in the native substrate to see how these new ligands compare to the original. | ||
| + | |||
| + | *Insert picture of the rescored ligands with the native ligand* | ||
Revision as of 11:14, 21 March 2022
This article is a continuation of PDBID 6ME2, with the previous one detailing how to run a virtual screen on this protein. This article will detail how to run a focused de novo design experiment on 6ME2.
Contents
I. De novo design
- Define and describe difference between focused and generic de novo design*
Generating a fragment library
Focused de novo growth
Focused de novo rescore
Now that we have generated our molecules from the de novo growth, we can rescore them based on different characteristics of the molecules in order to get a better idea of which ones are better for in vitro binding. In order to do this, make a directory called 012_dn_rescore and cd into it. We now need to generate an input file and a submit file. For the input file, vi into dn_rescore.in and write the following to that file:
conformer_search_type rigid use_internal_energy yes internal_energy_rep_exp 12 internal_energy_cutoff 100.0 ligand_atom_file ../58.dn_focus/dn_focus.out.denovo_build.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 yes contact_score_primary no contact_score_secondary no grid_score_primary no grid_score_secondary no multigrid_score_primary no multigrid_score_secondary no dock3.5_score_primary no dock3.5_score_secondary no continuous_score_primary no continuous_score_secondary no footprint_similarity_score_primary no footprint_similarity_score_secondary no pharmacophore_score_primary no pharmacophore_score_secondary no descriptor_score_primary yes descriptor_score_secondary no descriptor_use_grid_score no descriptor_use_multigrid_score no descriptor_use_continuous_score no descriptor_use_footprint_similarity yes descriptor_use_pharmacophore_score yes descriptor_use_tanimoto yes descriptor_use_hungarian yes descriptor_use_volume_overlap yes descriptor_fps_score_use_footprint_reference_mol2 yes descriptor_fps_score_footprint_reference_mol2_filename ../53.dock/6ME2.lig.min_scored.mol2 descriptor_fps_score_foot_compare_type Euclidean descriptor_fps_score_normalize_foot no descriptor_fps_score_foot_comp_all_residue yes descriptor_fps_score_receptor_filename ../50.structure/6ME2.receptor_wH.mol2 descriptor_fps_score_vdw_att_exp 6 descriptor_fps_score_vdw_rep_exp 12 descriptor_fps_score_vdw_rep_rad_scale 1 descriptor_fps_score_use_distance_dependent_dielectric yes descriptor_fps_score_dielectric 4.0 descriptor_fps_score_vdw_fp_scale 1 descriptor_fps_score_es_fp_scale 1 descriptor_fps_score_hb_fp_scale 0 descriptor_fms_score_use_ref_mol2 yes descriptor_fms_score_ref_mol2_filename ../53.dock/6ME2.lig.min_scored.mol2 descriptor_fms_score_write_reference_pharmacophore_mol2 no descriptor_fms_score_write_reference_pharmacophore_txt no descriptor_fms_score_write_candidate_pharmacophore no descriptor_fms_score_write_matched_pharmacophore no descriptor_fms_score_compare_type overlap descriptor_fms_score_full_match yes descriptor_fms_score_match_rate_weight 5.0 descriptor_fms_score_match_dist_cutoff 1.0 descriptor_fms_score_match_proj_cutoff 0.7071 descriptor_fms_score_max_score 20 descriptor_fingerprint_ref_filename ../53.dock/6ME2.lig.min_scored.mol2 descriptor_hms_score_ref_filename ../53.dock/6ME2.lig.min_scored.mol2 descriptor_hms_score_matching_coeff -5 descriptor_hms_score_rmsd_coeff 1 descriptor_volume_score_reference_mol2_filename ../53.dock/6ME2.lig.min_scored.mol2 descriptor_volume_score_overlap_compute_method analytical descriptor_weight_fps_score 1 descriptor_weight_pharmacophore_score 1 descriptor_weight_fingerprint_tanimoto -1 descriptor_weight_hms_score 1 descriptor_weight_volume_overlap_score -1 gbsa_zou_score_secondary no gbsa_hawkins_score_secondary no SASA_score_secondary no amber_score_secondary no minimize_ligand 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 chem_defn_file /gpfs/projects/AMS536/zzz.programs/dock6.9_release/parameters/chem.defn pharmacophore_defn_file /gpfs/projects/AMS536/zzz.programs/dock6.9_release/parameters/ph4.defn ligand_outfile_prefix descriptor.output write_footprints yes write_hbonds yes write_orientations no num_scored_conformers 1 rank_ligands no
Once you have finished, vi into dn_rescore.sh and write the following to that file:
#!/bin/bash #SBATCH --time=48:00:00 #SBATCH --nodes=1 #SBATCH --ntasks=28 #SBATCH --job-name=dn_rescore #SBATCH --output=dn_rescore.out #SBATCH -p long-28core
cd $SLURM_SUBMIT_DIR echo "starting Dock6.9 simulation" /gpfs/projects/AMS536/zzz.programs/dock6.9_release/bin/dock6.mpi -i dn_rescore.in -o dn_rescore.out
To submit this job, type the following into the terminal:
dock6 -i rescore.in -o rescore.out
When this finishes, you will generate a couple of files, the most important of which is the descriptor.output_scored.mol2 file. Move that to the comupter you are using Chimera on and load that file into Chimera using ViewDock as described in the virtual screen tutorial. It is also a good idea to load in the native substrate to see how these new ligands compare to the original.
- Insert picture of the rescored ligands with the native ligand*
