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

Scott Brozell sbrozell at rci.rutgers.edu
Thu Mar 24 00:19:34 PDT 2016


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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