[Dock-fans] Double bonds

Brian Fochtman brianfochtman at gmail.com
Sat Dec 17 13:39:46 PST 2016


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
>
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