[Dock-fans] auto-DUD-e and explicit water -- Dock 6.7

Jonathan Gough jonathan.d.gough at gmail.com
Thu Mar 24 10:14:21 PDT 2016


Does anyone know which of the DUDE sets has inputs for dock6.7?
Or can anyone recommend a set of comparable inputs/settings for getting
comparable results using dock6.7?

Explicitly I'm looking for recommendations on what one would use for the
dock6.7 equivalent of INDOCK and any recommendations on what scoring
function(s) I aught to use.

or how would they compare to the tutorial on the Risso Lav Tutorials page?
http://ringo.ams.sunysb.edu/index.php/2015_DOCK_tutorial_with_Poly(ADP-ribose)_polymerase_(PARP)#Large-vs.in

Thanks,
Jonathan

On Thu, Mar 24, 2016 at 3:19 AM, Scott Brozell <sbrozell at rci.rutgers.edu>
wrote:

> Hi,
>
> As far as the test diffs, they all look unsurprising and likely
> insignificant.
>
> scott
>
> On Wed, Mar 23, 2016 at 01:57:37PM -0400, Jonathan Gough wrote:
> > So,
> >
> > Maybe this is a difference between Dock3.7 and Dock6.7 (we only have 6.7)
> > and the nature of the system, but in docking the crystal_ligand.mol2 to a
> > receptor.mol2 (created from the receptor.pdb from DUDE) the best I can
> get
> > is an rmsd of 4 between the x-ray structure and the x-ray ligand. There
> are
> > even some poses that are almost on top of the water molecule (granted the
> > grid score is very high for those).
> >
> >
> > On a potentially related matter, I was looking at the internal tests and
> > there are differences that arise. The install instructions say that some
> > failures are OK, but in-case the errors are the reasons for the failure:
> > below are a few examples from the output of the difference comparison
> from
> > make check
> >
> > 96c96
> > < Lyr:1 Seg:0 12/60 retained, Pruning: 48-clustered
> > ---
> > > Lyr:1 Seg:0 11/60 retained, Pruning: 49-clustered
> > 102c102
> > <  Conformations:               12
> > ---
> > >  Conformations:               11
> >
> > ./anchor_and_grow/flex2.dockout.dif
> > 95c95
> > < Lyr:1 Seg:0 12/60 retained, Pruning: 48-clustered
> > ---
> > > Lyr:1 Seg:0 11/60 retained, Pruning: 49-clustered
> > 101c101
> > <  Conformations:               12
> > ---
> > >  Conformations:               11
> >
> > ./anchor_and_grow/flex4_scored.mol2.dif
> > 8,34c8,34
> > <       1 C1         24.    5.   61. C.3     1  <0>         0.
> > <       2 N1         24.    7.   61. N.4     1  <0>        -0.
> > <       3 C2         25.    8.   60. C.3     1  <0>         0.
> > <       4 C3         26.    8.   61. C.3     1  <0>        -0.
> > <       5 C4         26.    9.   62. C.3     1  <0>        -0.
> > <       6 C5         25.    8.   63. C.3     1  <0>        -0.
> > <       7 C6         23.    7.   62. C.3     1  <0>         0.
> > <       8 C7         23.    6.   63. C.3     1  <0>        -0.
> > <       9 Br1        21.    6.   62. Br      1  <0>        -0.
> > <      10 C8         23.    7.   60. C.3     1  <0>         0.
> > <      11 H1         24.    5.   61. H       1  <0>         0.
> > <      12 H2         25.    5.   60. H       1  <0>         0.
> > <      13 H3         25.    5.   62. H       1  <0>         0.
> > <      14 H4         25.    7.   59. H       1  <0>         0.
> > <      15 H5         24.    9.   60. H       1  <0>         0.
> > <      16 H6         27.    7.   61. H       1  <0>         0.
> > <      17 H7         27.    9.   61. H       1  <0>         0.
> > <      18 H8         27.    9.   63. H       1  <0>         0.
> > <      19 H9         25.   10.   62. H       1  <0>         0.
> > <      20 H10        25.    7.   63. H       1  <0>         0.
> > <      21 H11        24.    8.   64. H       1  <0>         0.
> > <      22 H12        23.    8.   62. H       1  <0>         0.
> > <      23 H13        23.    5.   63. H       1  <0>         0.
> > <      24 H14        22.    7.   64. H       1  <0>         0.
> > <      25 H15        22.    8.   60. H       1  <0>         0.
> > <      26 H16        23.    6.   59. H       1  <0>         0.
> > <      27 H17        22.    6.   60. H       1  <0>         0.
> > ---
> > >       1 C1         20.   12.   57. C.3     1  <0>         0.
> > >       2 N1         22.   12.   56. N.4     1  <0>        -0.
> > >       3 C2         21.   12.   55. C.3     1  <0>         0.
> > >       4 C3         21.   11.   54. C.3     1  <0>        -0.
> > >       5 C4         22.   10.   54. C.3     1  <0>        -0.
> > >       6 C5         22.   10.   55. C.3     1  <0>        -0.
> > >       7 C6         23.   11.   56. C.3     1  <0>         0.
> > >       8 C7         23.   10.   57. C.3     1  <0>        -0.
> > >       9 Br1        24.   12.   59. Br      1  <0>        -0.
> > >      10 C8         22.   13.   57. C.3     1  <0>         0.
> > >      11 H1         21.   11.   58. H       1  <0>         0.
> > >      12 H2         20.   12.   57. H       1  <0>         0.
> > >      13 H3         20.   11.   57. H       1  <0>         0.
> > >      14 H4         20.   13.   55. H       1  <0>         0.
> > >      15 H5         22.   13.   54. H       1  <0>         0.
> > >      16 H6         20.   11.   54. H       1  <0>         0.
> > >      17 H7         20.   12.   53. H       1  <0>         0.
> > >      18 H8         21.    9.   53. H       1  <0>         0.
> > >      19 H9         23.   11.   53. H       1  <0>         0.
> > >      20 H10        21.    9.   56. H       1  <0>         0.
> > >      21 H11        23.    9.   55. H       1  <0>         0.
> > >      22 H12        24.   11.   56. H       1  <0>         0.
> > >      23 H13        22.   10.   58. H       1  <0>         0.
> > >      24 H14        24.    9.   57. H       1  <0>         0.
> > >      25 H15        23.   13.   56. H       1  <0>         0.
> > >      26 H16        22.   14.   57. H       1  <0>         0.
> > >      27 H17        22.   13.   58. H       1  <0>         0.
> > 72,74c72,74
> > <       1 C1         21.    9.   60. C.2     1  <0>        -0.
> > <       2 C2         21.   10.   59. C.2     1  <0>        -0.
> > <       3 C3         23.   11.   60. C.2     1  <0>        -0.
> > ---
> > >       1 C1         21.   10.   59. C.2     1  <0>        -0.
> > >       2 C2         21.    9.   60. C.2     1  <0>        -0.
> > >       3 C3         21.    9.   62. C.2     1  <0>        -0.
> > 76,82c76,82
> > <       5 C4         21.    9.   62. C.2     1  <0>        -0.
> > <       6 C5         23.   11.   59. C.2     1  <0>         0.
> > <       7 O1         23.   12.   58. O.2     1  <0>        -0.
> > <       8 H1         20.    8.   60. H       1  <0>         0.
> > <       9 H2         21.   10.   58. H       1  <0>         0.
> > <      10 H3         21.    9.   63. H       1  <0>         0.
> > <      11 H4         24.   12.   60. H       1  <0>         0.
> > ---
> > >       5 C4         23.   11.   60. C.2     1  <0>        -0.
> > >       6 C5         21.    9.   63. C.2     1  <0>         0.
> > >       7 O1         20.    8.   63. O.2     1  <0>        -0.
> > >       8 H1         21.   10.   58. H       1  <0>         0.
> > >       9 H2         20.    8.   60. H       1  <0>         0.
> > >      10 H3         23.   11.   59. H       1  <0>         0.
> > >      11 H4         21.    9.   64. H       1  <0>         0.
> >
> > ./bump_filter/bump2.dockout.dif
> > 109c109
> > <  Conformations:               4
> > ---
> > >  Conformations:               6
> > 119c119
> > <  Conformations:               17
> > ---
> > >  Conformations:               16
> > 124c124
> > <  Conformations:               7
> > ---
> > >  Conformations:               8
> > 129c129
> > <  Conformations:               12
> > ---
> > >  Conformations:               11
> >
> > ./nchemgrid_GB_grid_generation/OUTCHEM.dif
> > 14,17c14,17
> > <    22.48       11.77       59.51
> > <  box x-dimension =    13.98
> > <  box y-dimension =    11.09
> > <  box z-dimension =    20.50
> > ---
> > >    22.489       11.777       59.515
> > >  box x-dimension =    13.984
> > >  box y-dimension =    11.097
> > >  box z-dimension =    20.503
> >
> >
> > On Wed, Mar 23, 2016 at 12:34 PM, Jonathan Gough <
> jonathan.d.gough at gmail.com
> > > wrote:
> >
> > > Thanks Dwight.
> > >
> > > On Wed, Mar 23, 2016 at 12:27 PM, Dwight McGee <dwight.mcgee at gmail.com
> >
> > > wrote:
> > >
> > >> Hi Jonathan,
> > >>
> > >> As a general of rule of thumb, for dealing with explicit waters that
> are
> > >> retained for docking purposes.  I make sure that the hydrogen atoms
> of the
> > >> receptor and water molecule are oriented correctly such that the
> distance
> > >> and angle meet the criteria that you set for a hydrogen bond. In
> addition,
> > >> we have run a short minimization with heavy restraints on the heavy
> atoms
> > >> in order to maximize the h-bond interactions. We visualized the
> minimized
> > >> structure just to make sure that the h-bond network is still
> maintained.
> > >>
> > >> Once satisfied we used that structure as our receptor for the docking
> > >> calculations.
> > >>
> > >> Hopefully, this helps when moving on to other systems once you are
> > >> successful with the pygm test case.
> > >>
> > >> Best,
> > >> Dwight
> > >>
> > >>
> > >> On Wed, Mar 23, 2016 at 12:06 PM, Trent E. Balius <tbalius at aol.com>
> > >> wrote:
> > >>
> > >>> Hi Jonathan,
> > >>>
> > >>> Question1.
> > >>>   A subset of the systems of the DUDE systems are distributed with
> > >>> SB2010/SB2012
> > >>>   which are prepared for DOCK6
> > >>>   Otherwise, you will need to prepare the receptors yourself,
> > >>>   I would suggest using Chimera and its dock prep tool to help you
> > >>> prepare the receptors.
> > >>>   I would also suggest using the mol2 file distributed with DUDE
> > >>> (audoDUDE is for DOCK3.7):
> > >>>      http://dude.docking.org/
> > >>>      here are the mol2 files:
> > >>>      http://dude.docking.org/targets/aa2ar/actives_final.mol2.gz
> > >>>      http://dude.docking.org/targets/aa2ar/decoys_final.mol2.gz
> > >>> Question2:
> > >>>   Including waters is possible in DOCK3.7 but a little tricky:
> > >>>   see the following:
> > >>>   http://wiki.bkslab.org/index.php/DOCK_3.7_tutorial_%28Anat%29
> > >>>   you will need to use "blastermaster.py -v --addNOhydrogensflag"
> > >>>
> > >>>   For dock6 it is a little easier,  you just need to make sure that
> the
> > >>> water
> > >>>   is in the mol2 file (and it has the right partial charges and atom
> > >>> type for grid to run properly).
> > >>>
> > >>> I hope that this helps,
> > >>>
> > >>> Trent
> > >>>
> > >>> ======================================
> > >>> Trent E. Balius, PhD
> > >>> Postdoc, Shoichet Lab,
> > >>> Dept. Pharm. Chem., UCSF
> > >>> Phone: (415) 514-4253
> > >>> URL: http://docking.org/~tbalius
> > >>> ======================================
> > >>>
> > >>>
> > >>> -----Original Message-----
> > >>> From: Jonathan Gough <jonathan.d.gough at gmail.com>
> > >>> To: Dwight McGee <dwight.mcgee at gmail.com>
> > >>> Cc: dock-fans <dock-fans at docking.org>
> > >>> Sent: Wed, Mar 23, 2016 7:28 am
> > >>> Subject: Re: [Dock-fans] auto-DUD-e and explicit water -- Dock 6.7
> > >>>
> > >>> Hi Dwight,
> > >>>
> > >>> Not exactly. At the moment, I am simply trying to reproduce the
> docking
> > >>> experiment for pygm. This is one of a few receptors in DUD-e that
> has an
> > >>> explicit water present in the receptor.pdb.
> > >>>
> > >>> http://dude.docking.org/targets/pygm
> > >>>
> > >>> In general, we are looking at explicit waters and water structure and
> > >>> would like to be able to use dock to run experiments with an
> explicit water
> > >>> (hence trying to reproduce pygm to make sure we know what we are
> doing).
> > >>>
> > >>> Any insight would be appreciated,
> > >>> Jonathan
> > >>>
> > >>> On Wed, Mar 23, 2016 at 10:16 AM, Dwight McGee <
> dwight.mcgee at gmail.com>
> > >>> wrote:
> > >>>
> > >>>> Hi Jonathan,
> > >>>>
> > >>>>
> > >>>> Pertaining to question #2. Are you trying to identify ligands that
> make
> > >>>> a specific water mediated interaction with the receptor?
> > >>>>
> > >>>> Best,
> > >>>> Dwight
> > >>>>
> > >>>> On Tue, Mar 22, 2016 at 7:17 PM, Jonathan Gough <
> > >>>> jonathan.d.gough at gmail.com> wrote:
> > >>>>
> > >>>>> Hi all,
> > >>>>>
> > >>>>> 2 questions -
> > >>>>>
> > >>>>> 1. I was wondering if it is possible to use the files for
> auto-DUD-E
> > >>>>> in testing for Dock 6.7. It seems as if everything is set up for
> 3.7, but
> > >>>>> not for 6.7.
> > >>>>>
> > >>>>> Related to that, I tried using basic steps in the tutorials to
> > >>>>> reproduce the binding of the x-ray crystal ligand from pygm (in
> the DUD-E)
> > >>>>> using the ligand.mol2 and the receptor.pdb from
> > >>>>> http://dude.docking.org/
> > >>>>>
> > >>>>> unfortunately, the generated poses were very far from expected.
> > >>>>>
> > >>>>> 2. when prepping the grid scoring function (or the pdb/mol2), is
> there
> > >>>>> something special that I need to do to ensure that the explicit
> water is
> > >>>>> treated correctly or to make sure that the water parameters are
> included?
>
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