[Dock-fans] use_clash_overlap and use_internal_energy

Jerry Parks jmp17 at duke.edu
Wed Jun 11 14:37:40 PDT 2008


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

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.



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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