[Dock-fans] Problems with Max_orientations and intramolecular clashes with Dock 6.2/DUD

Vidana.Epa at csiro.au Vidana.Epa at csiro.au
Tue May 12 21:59:44 PDT 2009


Hi all,

            Further to the Max_orientations problem that I reported yesterday (target: Neuraminidase, ligands from DUD database, flexible ligand docking with Dock 6.2), I took a molecule (ZINC03889009) that had been earlier docked with max_orientations set at 5000, and increased this value to 50000. To my surprise, it failed to dock, giving the error message "Could not complete growth. Confirm that the grid box is large enough to contain the ligand, and try increasing max_orientations". (!) I am puzzled as to how this could be.

            Then, when I inspected the earlier (i.e. max_iterations=5000) docking with this molecule, I find that there are serious steric clashes inside the molecule in the docked pose (absent in the input conformation), with a couple of non-bonded atoms just 0.35 A apart. So, the 'successful' docking is an error as well. Shouldn't the internal energy van der Waals term have prevented this from happening in the growth phase? As you can see from below, the input is pretty basic.

            Any suggestions/comments?

Thanks very much.

Cheers,

Vidana.


ligand_atom_file                                             dudp1lig_t3_1446.mol2
limit_max_ligands                                            no
skip_molecule                                                no
read_mol_solvation                                           no
calculate_rmsd                                               yes
use_rmsd_reference_mol                                       yes
rmsd_reference_filename                                      dudp1lig_t3_1446.mol2
orient_ligand                                                yes
automated_matching                                           yes
receptor_site_file                                           sphgen_cluster1_final.sph
max_orientations                                             5000
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                                            no
bump_filter                                                  yes
bump_grid_prefix                                             grid_r10
max_bumps_anchor                                             2
max_bumps_growth                                             2
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_r10
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                                                /software/dock6.2/parameters/vdw_AMBER_parm99.defn
flex_defn_file                                               /software/dock6.2/parameters/flex.defn
flex_drive_file                                              /software/dock6.2/parameters/flex_drive.tbl
ligand_outfile_prefix                                        dudp1lig_t6_1446c
write_orientations                                           no
num_scored_conformers                                        1
rank_ligands                                                 no





Vidana C. Epa

CSIRO,
Division of Molecular Health & Technologies,
343 Royal Parade,
Parkville, Victoria 3052,
AUSTRALIA.

tel: (61) - 3 - 9662 - 7345
fax:(61) - 3 - 9662 - 7347

email: Vidana.Epa at csiro.au

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