[Dock-fans] use_clash_overlap and use_internal_energy

Jerry Parks jmp17 at duke.edu
Thu Jun 12 14:49:56 PDT 2008


John

It definitely helps get reduce clashes if I increase clash_overlap from
0.5 to 1.0, but I still get some pretty close contacts. I guess I would
just expect a value of 1.0 to eliminate *all* vdw clashes/overlaps.

I've attached a couple of mol2 files that demonstrate the results.

Thanks,
Jerry


On Thu, 12 Jun 2008, John J. Irwin wrote:

> Hi Jerry
>
> In an email in dock-fans dated Mon Jul 24 12:07:30 2006, Kaushik
> suggests setting clash_overlap to a bigger number, maybe 1.0. I see you
> had it at 0.5. So, would you try 1.0 and let us know if that solves the
> problem? I do agree you should not see major clashes in docking output.
>
> Hope this helps
>
> John
>
>
>
>
>
> Jerry Parks wrote:
> > John
> >
> > All the results I mentioned in my previous email were obtained with DOCK
> > v6.2.
> >
> > You have a good point about just buying the compounds, but apparently our
> > experimental collaborators want to make at least some of them on their
> > own. I guess it's good synthesis practice for the grad students.
> >
> > So, do you see any obvious input file errors that could be fixed so that
> > we get more realistic geometries? Would we need to use AMBER Score to
> > prevent the intramolecular ligand clashes?
> >
> > Thanks,
> > Jerry
> >
> > On Wed, 11 Jun 2008, John J. Irwin wrote:
> >
> >
> >> 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
> >>>
> >>> _______________________________________________
> >>> Dock-fans mailing list
> >>> Dock-fans at docking.org
> >>> http://blur.compbio.ucsf.edu/mailman/listinfo/dock-fans
> >>>
> >>>
>
-------------- next part --------------
@<TRIPOS>MOLECULE
ZINC04262355
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SMALL
GASTEIGER
Energy = 0

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     66 O5         10.9786   10.4811   35.7604 O.co2   1  <0>1       -0.7493
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@<TRIPOS>SUBSTRUCTURE
     1 <0>1        1 TEMP              0 ****  ****    0 ROOT


########## Name:		ZINC04474014
##########    Grid Score:          -58.060341
##########           vdw:          -47.305569
##########            es:          -10.754770

-------------- next part --------------

########## Name:		ZINC04262355
##########    Grid Score:          -62.366383
##########           vdw:          -49.247429
##########            es:          -13.118955

@<TRIPOS>MOLECULE
ZINC04262355
 66 68 1 0 0
SMALL
GASTEIGER
Energy = 0

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@<TRIPOS>SUBSTRUCTURE
     1 <0>1        1 TEMP              0 ****  ****    0 ROOT



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