[Dock-fans] Protein-Protein Docking

[Scott Brozell]

Hi,

On Mon, 1 Sep 2008, CJ Arthur wrote:

> I've been trying to dock two proteins using Dock and have hit some
> problems. If possible could someone have a look at what I'm doing an tell
> me what I'm doing wrong please.

http://dock.compbio.ucsf.edu/DOCK_6/dock6_manual.htm#MacromolecularDocking
Grepping for ligand_center and match_receptor in the source code 
finds only lines in program grid.
Grepping for use_ligand_spheres and ligand_sphere_file in the source code 
finds only lines in program dock.

Thus, Macromolecular Docking as described in the manual appears
to need both corrections (ligand_centers -> use_ligand_spheres,
ligand_center_file -> ligand_sphere_file, and match_receptor_sites seems
to have been redundant and merely replaced with automated_matching=no)
and completion (there may be steps involving grid that are not described).

I'm adding an investigation of this to the todo list.
But maybe the grid clues are enough for you to figure this out.
Unfortunately, it looks like the only documentation for this aspect of grid
is its source code.
Also I may be all wrong regarding grid.  I've never tried macromolecular
DOCKing.  As a final thought, start small and scale up.

Please follow up since I want to at least correct the documentation
such as it is.
Good luck,
Scott


> Can anyone see what I'm doing wrong, or can someone send me the grid and
> dock input files that they have used previously so that i can try to get
> an idea of where i'm making my mistake.
> 
> Thanks in advance.
> 
> Chris
> 
> I generate spheres around both my recetor and ligand proteins using sphgen
> 
> i then select spheres around the active site of the receptor, so that the
> ligand is placed in an appropriate place
> 
> sphere_selector receptor.sph activesite.mol2 10.0
> 
> and make a pdb file of selected_spheres.sph so that i can check it in chimera
> showsphere
> 
> i then use showbox with a margin of 50A, so that its big enought to hold
> my ligand molecule.
> 
> I then use grid with the grid input settings listed below
> 
> And then I dock using the dock settings listed below.
> 
> What happens is that the ligand molecule is overlayed over the receptor
> (its as iff the the ligand is put 'into' the spheres of the receptor.
> 
> 
> 
> *******
> grid input
> 
> compute_grids          yes
> grid_spacing           0.3
> output_molecule        no
> contact_score          no
> energy_score           yes
> energy_cutoff_distance 9999
> atom_model             a
> attractive_exponent    6
> repulsive_exponent     12
> distance_dielectric    yes
> dielectric_factor      4
> bump_filter            yes
> bump_overlap           0.75
> receptor_file          receptor.mol2
> box_file               site_box.pdb
> vdw_definition_file    /home/chxcja/dock6/parameters/vdw_AMBER_parm99.defn
> score_grid_prefix      grid
> 
> 
> 
> *****
> dock input
> 
> ligand_atom_file                                             ligand.mol2
> limit_max_ligands                                            no
> skip_molecule                                                no
> read_mol_solvation                                           no
> calculate_rmsd                                               no
> orient_ligand                                                yes
> automated_matching                                           no
> distance_tolerence                                           0.25
> distance_minimum                                             2.0
> nodes_minimum                                                3
> nodes_maximum                                                10
> receptor_site_file                                           activesite.sph
> max_orientations                                             500
> critical_points                                              no
> chemical_matching                                            no
> use_ligand_spheres                                           yes
> ligand_sphere_file                                           ligand.sph
> flexible_ligand                                              no
> bump_filter                                                  yes
> bump_grid_prefix                                             grid
> max_bumps_anchor                                             1
> max_bumps_growth                                             1
> score_molecules                                              yes
> contact_score_primary                                        no
> contact_score_secondary                                      no
> grid_score_primary                                           no
> grid_score_secondary                                         yes
> grid_score_rep_rad_scale                                     1
> grid_score_vdw_scale                                         1
> grid_score_es_scale                                          1
> grid_score_grid_prefix                                       grid
> dock3.5_score_primary                                        no
> continuous_score_primary                                     yes
> cont_score_rec_filename                                      receptor.mol2
> cont_score_att_exp                                           6
> cont_score_rep_exp                                           12
> cont_score_rep_rad_scale                                     1
> cont_score_use_dist_dep_dielectric                           yes
> cont_score_dielectric                                        4.0
> cont_score_vdw_scale                                         1
> cont_score_es_scale                                          1
> minimize_ligand                                              no
> atom_model                                                   all
> vdw_defn_file
> /home/chxcja/dock6/parameters/vdw_AMBER_parm99.defn
> flex_defn_file
> /home/chxcja/dock6/parameters/flex.defn
> flex_drive_file
> /home/chxcja/dock6/parameters/flex_drive.tbl
> ligand_outfile_prefix                                        complex_out
> write_orientations                                           yes
> num_primary_scored_conformers_rescored                       10
> write_primary_conformations                                  yes
> cluster_primary_conformations                                yes
> cluster_rmsd_threshold                                       2.0
> num_clusterheads_for_rescore                                 5
> num_secondary_scored_conformers                              5
> write_secondary_conformations                                yes
> rank_primary_ligands                                         no
> rank_secondary_ligands                                       no
> 
> ******
>