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

Jonathan Gough jonathan.d.gough at gmail.com
Wed Mar 23 10:57:37 PDT 2016


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?
>>>>>
>>>>> Thanks,
>>>>> Jonathan
>>>>>
>>>>> _______________________________________________
>>>>> Dock-fans mailing list
>>>>> Dock-fans at docking.org
>>>>> http://mailman.docking.org/mailman/listinfo/dock-fans
>>>>>
>>>>>
>>>>
>>>>
>>>> --
>>>> T. Dwight McGee Jr.
>>>>
>>>> dwight.mcgee at gmail.com
>>>>
>>>> "Problems cannot be solved at the same level of awareness that created
>>>> them."
>>>>                 Albert Einstein
>>>>
>>>
>>> _______________________________________________
>>> Dock-fans mailing list
>>> Dock-fans at docking.org
>>> http://mailman.docking.org/mailman/listinfo/dock-fans
>>>
>>
>>
>>
>> --
>> T. Dwight McGee Jr.
>>
>> dwight.mcgee at gmail.com
>>
>> "Problems cannot be solved at the same level of awareness that created
>> them."
>>                 Albert Einstein
>>
>
>
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