[Dock-fans] Double bonds

Maciek Wójcikowski maciek at wojcikowski.pl
Sun Dec 18 02:39:15 PST 2016


Hi all,

You can explicitly disable double bonds being rotatable in definition file
"flex.defn" [see
http://dock.compbio.ucsf.edu/DOCK_6/dock6_manual.htm#flexdefn ].

----
Pozdrawiam,  |  Best regards,
Maciek Wójcikowski
maciek at wojcikowski.pl

2016-12-17 23:09 GMT+01:00 James Foster (PG Research) <
j.r.foster at dundee.ac.uk>:

> Thank you Brian, this worked an absolute treat. Hope you have a great
> Christmas!
>
>
> James
> ------------------------------
> *From:* Brian Fochtman <brianfochtman at gmail.com>
> *Sent:* 17 December 2016 21:39:46
> *To:* James Foster (PG Research); dock-fans at docking.org
>
> *Subject:* Re: [Dock-fans] Double bonds
>
> Hey,
> I was able to recreate the behavior you are seeing when docking your
> ligand into an arbitrary structure I had available.  Sorry I sent you on a
> goose chase - the script I sent had a bug.  I've included an updated
> version of the script and confirmed that after docking the cis-double bonds
> are preserved.
>    - Brian
>
> On Sat, Dec 17, 2016 at 3:51 PM, James Foster (PG Research) <
> j.r.foster at dundee.ac.uk> wrote:
>
>> Ah yes, that's a good point. As you can probably tell I'm new to
>> docking..
>>
>>
>> I'm trying to see if its possible to dock 2-arachidonoylglycerol against
>> the recent CB2 receptor crystal structure. I know a c-shaped binding mode
>> was made by the authors of the paper, but I'd like to see
>> if dock can make a similar prediction.
>>
>>
>> James
>>
>>
>> ------------------------------
>> *From:* Brian Fochtman <brianfochtman at gmail.com>
>> *Sent:* 17 December 2016 20:02:23
>>
>> *To:* James Foster (PG Research)
>> *Subject:* Re: [Dock-fans] Double bonds
>>
>> James,
>>     No problem.  A couple things.
>> 1. Unrelated to the double bond issue is that you don't have partial
>> charges on your small molecule and therefore are not considering
>> electrostatic interactions - is this by design?
>> 2. I'm really confused by this double bond issue.  DOCK has no way of
>> removing atoms or bonds so I'm unclear of what is happening here.  It makes
>> sense that if you post process the anchor_and_grow.mol2 file you sent you
>> would get the final_output_scored.mol2 file you sent.  If you want to send
>> over your protein structure I can rerun your calculation and see if I get
>> the same issue.
>> -Brian
>>
>> On Sat, Dec 17, 2016 at 12:34 PM, James Foster (PG Research) <
>> j.r.foster at dundee.ac.uk> wrote:
>>
>>> Hi Brian,
>>>
>>> Thank you for sticking with me on this issue. I think I understand the
>>> rationale behind what we're trying to do. On the temp_for_docking.mol2 file
>>> I can see the fake rings have been added and the double bonds are all cis
>>> as they should be. But when I run the anchor and grow script the
>>> output file (anchor_and_grow_scored.mol2) has trans bonds and the fake
>>> rings have gone. Then when I run the python script using the
>>> "anchor_and_grow_scored.mol2" file the fake rings have been added again?
>>>
>>>
>>> Please find attached pictures of the same double bond at each step of
>>> the process, and my 'anchor_and grow_scored.mol2 file.
>>>
>>>
>>> Thanks,
>>>
>>> James
>>>
>>> ------------------------------
>>> *From:* Brian Fochtman <brianfochtman at gmail.com>
>>> *Sent:* 17 December 2016 14:34:54
>>>
>>> *To:* James Foster (PG Research)
>>> *Subject:* Re: [Dock-fans] Double bonds
>>>
>>> Hey James,
>>> What the script does is draw fake rings about double bonds, as dock
>>> doesn't sample torsion angles in rings.  This results in docked molecules
>>> with with same torsion angles around double bonds that you started with.
>>>
>>> temp.for.docking.mol2 had these rings which is exactly what we want.
>>>
>>> anchor_and_grow_scored.mol2 should also have these rings.
>>>
>>> When running
>>> python 2014.05...cyclize_db.py anchor_and_grow_scored.mol2
>>>  final_output_scored.mol2 we should have a final...mol2 file without rings
>>> but the final...mol2 file you sent is cyclized. (The same script removes
>>> these artificial rings when it finds them.)
>>>
>>> My guess is that your input for the second python step isn't using the
>>> newly generated anchor_and_grow_scored.mol2.
>>>
>>> To test this we need to take a look at anchor_and_grow_scored.mol2.
>>>
>>> If this ends up being right I'd like to run the docking myself.
>>>
>>> Hope this helps.
>>> -Brian
>>>
>>> On Dec 17, 2016 5:02 AM, "James Foster (PG Research)" <
>>> j.r.foster at dundee.ac.uk> wrote:
>>>
>>>> Sorry Brian, that was from a different dock. Please find attached the
>>>> right file..
>>>> ------------------------------
>>>> *From:* Brian Fochtman <brianfochtman at gmail.com>
>>>> *Sent:* 17 December 2016 00:45:33
>>>> *To:* James Foster (PG Research)
>>>> *Subject:* Re: [Dock-fans] Double bonds
>>>>
>>>> I think the issue is that you didn't set  "ligand_atom_file" as
>>>> "temp_for_docking.mol2" in your dock.in file.
>>>>
>>>> >From dock.out:
>>>>
>>>> Molecule Library Input Parameters
>>>> ------------------------------------------------------------
>>>> ------------------------------
>>>> ligand_atom_file
>>>> /Users/jdogg/Desktop/gloriamg2a/linoacid.mol2
>>>> limit_max_ligands                                            no
>>>>
>>>>
>>>>
>>>> On Fri, Dec 16, 2016 at 7:28 PM, James Foster (PG Research) <
>>>> j.r.foster at dundee.ac.uk> wrote:
>>>>
>>>>> Oops sorry, is this the right one?
>>>>> ------------------------------
>>>>> *From:* Brian Fochtman <brianfochtman at gmail.com>
>>>>> *Sent:* 17 December 2016 00:04:43
>>>>>
>>>>> *To:* James Foster (PG Research)
>>>>> *Subject:* Re: [Dock-fans] Double bonds
>>>>>
>>>>> Sorry should have been more clear. The non mol2 output from dock.
>>>>> Example if you run dock like
>>>>> dock -i dock.in* -o dock.out *
>>>>>
>>>>> I would like to see the *dock.out* file.
>>>>>
>>>>> On Fri, Dec 16, 2016 at 7:01 PM, James Foster (PG Research) <
>>>>> j.r.foster at dundee.ac.uk> wrote:
>>>>>
>>>>>> Please see attached :)
>>>>>> ------------------------------
>>>>>> *From:* Brian Fochtman <brianfochtman at gmail.com>
>>>>>> *Sent:* 16 December 2016 23:48:03
>>>>>> *To:* James Foster (PG Research)
>>>>>> *Subject:* Re: [Dock-fans] Double bonds
>>>>>>
>>>>>> Sorry, also your dock.out file.
>>>>>>
>>>>>> On Fri, Dec 16, 2016 at 6:26 PM, James Foster (PG Research) <
>>>>>> j.r.foster at dundee.ac.uk> wrote:
>>>>>>
>>>>>>> Sure, please find attached..
>>>>>>> ------------------------------
>>>>>>> *From:* Brian Fochtman <brianfochtman at gmail.com>
>>>>>>> *Sent:* 16 December 2016 22:19:36
>>>>>>>
>>>>>>> *To:* James Foster (PG Research)
>>>>>>> *Cc:* dock-fans at docking.org
>>>>>>> *Subject:* Re: [Dock-fans] Double bonds
>>>>>>>
>>>>>>> Can you send your mol2 files?
>>>>>>>
>>>>>>> On Fri, Dec 16, 2016 at 3:56 PM, James Foster (PG Research) <
>>>>>>> j.r.foster at dundee.ac.uk> wrote:
>>>>>>>
>>>>>>>> Hi Brian,
>>>>>>>>
>>>>>>>>  Thanks very much for the reply. I tried preparing the molecule
>>>>>>>> with your script, running a flexible docking algorithm and then post
>>>>>>>> processing the output file your script but the double bonds still
>>>>>>>> come out as trans instead of remaining cis? Maybe it's not right
>>>>>>>> to use a flexible docking algorithm on a molecule containing a long
>>>>>>>> alkyl chain with double bonds?
>>>>>>>>
>>>>>>>>
>>>>>>>> Thanks again,
>>>>>>>>
>>>>>>>> James
>>>>>>>> ------------------------------
>>>>>>>> *From:* Brian Fochtman <brianfochtman at gmail.com>
>>>>>>>> *Sent:* 16 December 2016 03:18:41
>>>>>>>> *To:* James Foster (PG Research)
>>>>>>>> *Cc:* dock-fans at docking.org
>>>>>>>> *Subject:* Re: [Dock-fans] Double bonds
>>>>>>>>
>>>>>>>> Hi Jim,
>>>>>>>>      There are a couple ways to to change this behavior within
>>>>>>>> DOCK.  The method I prefer is as follows:
>>>>>>>>
>>>>>>>>      I've attached a script that should be used to pre and post
>>>>>>>> process your molecules.
>>>>>>>>
>>>>>>>>       1.   python     2014.05.16_cyclize_db.py
>>>>>>>> input.mol2      temp_for_docking.mol2
>>>>>>>>       2.   run dock as you normally would except specify
>>>>>>>> "temp_for_docking.mol2" from above as the ligand_atom_file
>>>>>>>>       3.   python      2014.05.16_cyclize_db.py
>>>>>>>> output_scored.mol2       final_output_scored.mol2
>>>>>>>>
>>>>>>>>
>>>>>>>>      What this process does is lock all double bonds in the
>>>>>>>> molecule in the original conformations.  Running the script the second time
>>>>>>>> cleans up the output file.  One disadvantage of this process is that RMSDs
>>>>>>>> have to be calculated after the face on final_output_scored.mol2.    Let me
>>>>>>>> know if you have any questions or need help getting the script running.
>>>>>>>>
>>>>>>>> -Brian
>>>>>>>>
>>>>>>>>
>>>>>>>> On Thu, Dec 15, 2016 at 6:52 PM, James Foster (PG Research) <
>>>>>>>> j.r.foster at dundee.ac.uk> wrote:
>>>>>>>>
>>>>>>>>> Hello,
>>>>>>>>>
>>>>>>>>> I’ve tried using rigid and flexible docking to dock a molecule
>>>>>>>>> containing a cis c-c double bond. After running the dock the conformation
>>>>>>>>> of the bond turns into trans? Please do you know of any solution to correct
>>>>>>>>> this?
>>>>>>>>> Thanks,
>>>>>>>>> Jim
>>>>>>>>>
>>>>>>>>> The University of Dundee is a registered Scottish Charity, No:
>>>>>>>>> SC015096
>>>>>>>>>
>>>>>>>>> _______________________________________________
>>>>>>>>> Dock-fans mailing list
>>>>>>>>> Dock-fans at docking.org
>>>>>>>>> http://mailman.docking.org/mailman/listinfo/dock-fans
>>>>>>>>>
>>>>>>>>>
>>>>>>>>
>>>>>>>> The University of Dundee is a registered Scottish Charity, No:
>>>>>>>> SC015096
>>>>>>>>
>>>>>>>
>>>>>>>
>>>>>>> The University of Dundee is a registered Scottish Charity, No:
>>>>>>> SC015096
>>>>>>>
>>>>>>
>>>>>>
>>>>>> The University of Dundee is a registered Scottish Charity, No:
>>>>>> SC015096
>>>>>>
>>>>>
>>>>>
>>>>> The University of Dundee is a registered Scottish Charity, No: SC015096
>>>>>
>>>>
>>>>
>>>> The University of Dundee is a registered Scottish Charity, No: SC015096
>>>>
>>>
>>> The University of Dundee is a registered Scottish Charity, No: SC015096
>>>
>>
>>
>> The University of Dundee is a registered Scottish Charity, No: SC015096
>>
>
>
> The University of Dundee is a registered Scottish Charity, No: SC015096
>
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