[Dock-fans] use_clash_overlap and use_internal_energy

[John J. Irwin]

Hi Jerry

Are you using the latest version, DOCK 6.2 ?

I hope you will not have to synthesize compounds, but just buy them. 
That is the whole point of ZINC - to shorten the hypothesis-test cycle.

Good luck.

John


Jerry Parks wrote:
> Hello
>
> We have been using anchor-and-grow to perform flexible docking and
> minimization on a large number of compounds from the zinc7 database. Many
> of the highest scoring compounds suffer from geometries with unreasonable,
> overlapping functional groups and rings. I really don't think we can trust
> the results we've obtained thus far.
>
> Our goal is to generate leads via docking, then synthesize approximately
> 20-50 molecules and assay them to determine if they are in fact
> inhibitors.
>
> I have seen previous posts regarding "interpenetrated" structures, etc.,
> but I'm still not sure how to circumvent this problem. It seems to me that
> use_internal_energy should prevent these types of overlaps if the
> repulsive vdw exponent is in effect. Any help/advice would be appreciated.
>
> I have attached a representative input file below.
>
> Thanks,
> Jerry
>
> --------------------
>
> ligand_atom_file                     test-8.mol2
> limit_max_ligands                    no
> skip_molecule                        no
> read_mol_solvation                   no
> calculate_rmsd                       no
> orient_ligand                        yes
> automated_matching                   yes
> receptor_site_file                   ../selected_spheres.sph
> max_orientations                     500
> critical_points                      no
> chemical_matching                    no
> use_ligand_spheres                   no
> flexible_ligand                      yes
> min_anchor_size                      40
> pruning_use_clustering               yes
> pruning_max_orients                  100
> pruning_clustering_cutoff            100
> use_internal_energy                  yes
> internal_energy_att_exp              6
> internal_energy_rep_exp              12
> internal_energy_dielectric           4.0
> use_clash_overlap                    yes
> clash_overlap                        0.50
> 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_999_10
> 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_final_min                    no
> 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                test-8
> write_orientations                   no
> num_scored_conformers_written        1
> rank_ligands                         yes
> max_ranked_ligands                   500
>
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