[Dock-fans] use_clash_overlap and use_internal_energy

John J. Irwin jji at cgl.ucsf.edu
Thu Jun 12 13:35:58 PDT 2008


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
>>>
>>>       


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