[Dock-fans] Missing Scores [signed]

M. A. Lardy [c] lardy at chemistry.ucsc.edu
Mon Apr 11 11:47:55 PDT 2005


Terry,

Well after setting flexible_ligand to no, I do get scores for my  
compounds.  Although, they are all 10000 (that must be a default value  
for the maximum for sterical hindered binding scores).  The active site  
might be too constrained, but both the protein and three of ligands  
that I have been attempting to reposition are from crystal structure  
and have less than three rotatable bonds.  Anyway, I am going to try  
some of the suggestions that I have received from this list today, and  
let you all know what ended up working out.

Thanks again,
Matthew

On Apr 7, 2005, at 3:48 PM, Terry Lang wrote:

> Dear Matthew,
>
>   If you don't get a response at the end of your run, it is because,  
> for some reason, DOCK did not consider any of the generated poses to  
> have reasonable scores.  We know that it is confusing that nothing is  
> being printed out in the output file and are working to fix that, at  
> which point we will post a bugfix on the web page.
>   For your particular case, because you do have orientations but do  
> not have conformations, you most likely did not get any scored poses  
> because anchor and grow could not find any conformations with  
> reasonable internal energies or reasonable interaction energies.  This  
> generally happens when a) your small molecule has > 7 rotatable bonds  
> or b) your active site is buried or in other ways very sterically  
> restricted.  In order to validate that the problem is actually the  
> flexible ligand sampling, you can perform a rigid dock run (set  
> "flexible_ligand" to no) and see if you get out answers.
>   In order to deal with the sampling issue (if this is indeed the  
> problem), you can either try conformational expansion of your  
> ligand/library prior to docking and then keep your ligands rigid.  You  
> can also try to run either minimizations or md simulations of your  
> receptor-ligand complex to see if you can make your active site less  
> sterically restricted.
>   Please let me know whether this solves your problem.
>
> Good luck,
> Terry
>
>
> At 04:06 PM 4/6/2005, M. A. Lardy [c] wrote:
>> Hi all,
>>
>> I am having difficulty getting the scores out of docking runs.  I am
>> running Dock v5.2.0, and this is what I see from the run:
>>
>>
>> --------------------------------------
>> DOCK v5.2.0-Beta
>>
>> Released March 2005
>> Copyright UCSF
>> Authored by:
>>         Tack Kuntz
>>         Demetri Moustakas
>>         Paula Therese Lang
>>         Scott Pegg
>> --------------------------------------
>>
>>
>> Molecule Library Parameters
>> ---------------------------------------------------------------------- 
>> -- ------------------
>> ligand_atom_file
>> 23ligands.mol2
>> ligand_outfile_prefix                                        sertanty
>> limit_max_ligands                                            no
>> write_orientations                                           yes
>> write_conformations                                          yes
>> initial_skip                                                 0
>> calculate_rmsd                                               yes
>> use_rmsd_reference_mol
>> 23ligands.mol2
>> rank_ligands                                                 yes
>> max_ranked_ligands                                           500
>> scored_mol_output_override                                   no
>>
>> Orient Ligand Parameters
>> ---------------------------------------------------------------------- 
>> -- ------------------
>> orient_ligand                                                yes
>> automated_matching                                           yes
>> receptor_site_file
>> /home/lardy/research2/ucn01pocket/1nvqunbound.sph
>> max_orientations                                             1000
>> critical_points                                              no
>> chemical_matching                                            no
>> use_ligand_spheres                                           no
>>
>> Flexible Ligand Parameters
>> ---------------------------------------------------------------------- 
>> -- ------------------
>> flexible_ligand                                              yes
>>
>> Anchor & Grow Parameters
>> ---------------------------------------------------------------------- 
>> -- ------------------
>> ag_conf_search                                               yes
>> min_anchor_size                                              50
>> num_anchor_poses                                             50
>> number_confs_per_cycle                                       50
>> 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 Parameters
>> ---------------------------------------------------------------------- 
>> -- ------------------
>> bump_filter                                                  yes
>> bump_grid_prefix                                             grid
>> max_bumps                                                    2
>>
>> Master Score Parameters
>> ---------------------------------------------------------------------- 
>> -- ------------------
>> score_molecules                                              yes
>>
>> Energy Score Parameters
>> ---------------------------------------------------------------------- 
>> -- ------------------
>> energy_score_primary                                         yes
>> energy_score_secondary                                       yes
>> vdw_scale                                                    1
>> es_scale                                                     1
>> nrg_grid_prefix                                              grid
>>
>> Simplex Minimization Parameters
>> ---------------------------------------------------------------------- 
>> -- ------------------
>> minimize_ligand                                              yes
>> minimize_anchor                                              yes
>> minimize_flexible_growth                                     yes
>> minimize_final_pose                                          yes
>> use_advanced_simplex_parameters                              yes
>> simplex_anchor_min_max_iterations                            50
>> simplex_anchor_min_max_cycles                                1
>> simplex_anchor_min_score_converge                            0.1
>> simplex_anchor_min_cycle_converge                            1.0
>> simplex_anchor_min_trans_step                                1.0
>> simplex_anchor_min_rot_step                                  0.1
>> simplex_anchor_min_tors_step                                 10.0
>> simplex_flex_min_max_iterations                              10
>> simplex_flex_min_max_cycles                                  1
>> simplex_flex_min_score_converge                              0.1
>> simplex_flex_min_cycle_converge                              1.0
>> simplex_flex_min_trans_step                                  1.0
>> simplex_flex_min_rot_step                                    0.1
>> simplex_flex_min_tors_step                                   10.0
>> simplex_final_min_max_iterations                             100
>> simplex_final_min_max_cycles                                 1
>> simplex_final_min_score_converge                             0.1
>> simplex_final_min_cycle_converge                             1.0
>> simplex_final_min_trans_step                                 1.0
>> simplex_final_min_rot_step                                   0.1
>> simplex_final_min_tors_step                                  10.0
>> simplex_random_seed                                          0
>>
>> Atom Typing Parameters
>> ---------------------------------------------------------------------- 
>> -- ------------------
>> atom_model                                                   all
>> vdw_defn_file
>> /usr/local/software/dock/dock.5.2_linux/parameters/  
>> vdw_AMBER_parm94.defn
>> flex_defn_file
>> /usr/local/software/dock/dock.5.2_linux/parameters/flex.defn
>> flex_drive_file
>> /usr/local/software/dock/dock.5.2_linux/parameters/flex_drive.tbl
>> chem_defn_file
>> /usr/local/software/dock/dock.5.2_linux/parameters/chem.defn
>> ---------------------------------------------------------------------- 
>> -- ------------------
>>
>> Initializing Library File Routines...
>> Initializing Orienting Routines...
>> Initializing Conformer Generator Routines...
>> Initializing Bump Filter Routines...
>>  Reading the bump grid from grid.bmp
>> Initializing Energy Score Routines...
>>  Reading the energy grid from grid.nrg
>>
>>
>> 23 Molecules Processed
>> Elapsed time:   56.82 seconds
>>
>> It appears to me that the run was successful, but when I open the
>> sertanty prefix files, they are all empty with one exception.  The
>> exception being that the sertanty_orient.mol2 has structures.  Am I
>> missing something?  I am more than happy to share any other  
>> information
>> that might be relevant to this problem.
>>
>> Thanks,
>> Matthew
>>
>>
>
>>
>> _______________________________________________
>> Dock-fans mailing list
>> Dock-fans at docking.org
>> http://blur.compbio.ucsf.edu/mailman/listinfo/dock-fans
>
> ***NOTE:  This is a new e-mail address (terry at cgl.ucsf.edu)  Please  
> update your address book!***
>
> P. Therese (Downing) Lang
> Kuntz and James Labs
> UCSF - CCB Graduate Program
> Phone:  (415)476-3986
>
>


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