[gmx-users] ligand moving out during umbrella sampling

Justin Lemkul jalemkul at vt.edu
Sun May 21 16:43:48 CEST 2017



On 5/21/17 9:47 AM, abhisek Mondal wrote:
> I did try the code successfully on a configuration generated after pulling.
> The NVT approach with direction-periodic geometry worked nicely for the
> particular configuration.
>
> However, when I tried to reapply the same code (with modified COMs and thus
> pull_vec) on a different configuration, something awkward happened. The
> ligand got pulled through protein and got stuck inside it. I have put the
> trajectory movie alongwith md_umbrella.mdp file here:
> https://drive.google.com/drive/folders/0B6O-L5Y7BiGJQ1FIc2tIRFE2dE0
>
> Would you please care to give some advise regarding this odd behavior.
>

Likely some elements of your setup are inadequate.  You have a large, flexible 
ligand, so perhaps using its overall COM is inappropriate.  You're also using 
the entire protein COM as the other end of the reaction coordinate, and perhaps 
that's not good enough (I've suggested a number of times to be judicious in the 
choice of residues taken as the group corresponding to the protein, but it seems 
you're simply not doing that so I'll stop suggesting it).  Perhaps your pull 
vector is calculated incorrectly.  A lot going on.  Back up and do something 
simpler, a test case that is easy to define so you can get comfortable with 
setting these things up and understanding/diagnosing weird behavior.

-Justin

> Thank you.
>
> On Fri, May 19, 2017 at 5:18 PM, Justin Lemkul <jalemkul at vt.edu> wrote:
>
>>
>>
>> On 5/19/17 5:56 AM, abhisek Mondal wrote:
>>
>>> On Thu, May 18, 2017 at 6:48 PM, Justin Lemkul <jalemkul at vt.edu> wrote:
>>>
>>>
>>>>
>>>> On 5/17/17 8:55 AM, abhisek Mondal wrote:
>>>>
>>>> This time I think I got ligand restrained successfully during the
>>>>> umbrella
>>>>> sampling. I have removed the restrain from protein, as per your advice.
>>>>> Defined the COM vector in md_umbrella.mdp, applied pull_k1=1000 and used
>>>>> pull_rate1=0.0.
>>>>> I have uploaded the trajectory movie (and other mdp files) in the
>>>>> following
>>>>> link:
>>>>> https://drive.google.com/drive/folders/0B6O-L5Y7BiGJQ1FIc2tIRFE2dE0
>>>>>
>>>>> However, I'm facing a problem. Due to the withdrawal of the position
>>>>> restrain of protein. The protein and ligand (together) is moving around
>>>>> the
>>>>> box and resulting in "Distance of pull group 1 (10.441990 nm) is larger
>>>>> than 0.49 times the box size (10.646989)" error.
>>>>>
>>>>> As per the video I have uploaded, if I assume this approach worked, then
>>>>> how can I avoid this error ? Is  there any way to make sure the
>>>>> protein-ligand remains in the middle of the box (or nearby). I have
>>>>> taken
>>>>> pretty large box compared to the protein structure from the beginning.
>>>>>
>>>>> Please suggest me a way out.
>>>>>
>>>>>
>>>>> Use a larger box or use direction-periodic geometry.
>>>>
>>>
>>>
>>>  For the sake of computational power I'm leaning towards
>>> direction-periodic
>>> geometry. However, from the mailing list entries I found out that pressure
>>> coupling should not be used for this kind of geometry setup.
>>> NVT coupling with no velocity generation is what I'm opting for. There are
>>> a lot of doubt regarding the md_umbrella.mdp setup using NVT protocol.
>>> Would you please suggest if the code (
>>> https://drive.google.com/drive/folders/0B6O-L5Y7BiGJQ1FIc2tIRFE2dE0)
>>> looks
>>> sensible ?
>>>
>>> Eagerly waiting for your opinion.
>>>
>>>
>> Try it and see what happens.
>>
>> -Justin
>>
>> --
>> ==================================================
>>
>> Justin A. Lemkul, Ph.D.
>> Ruth L. Kirschstein NRSA Postdoctoral Fellow
>>
>> Department of Pharmaceutical Sciences
>> School of Pharmacy
>> Health Sciences Facility II, Room 629
>> University of Maryland, Baltimore
>> 20 Penn St.
>> Baltimore, MD 21201
>>
>> jalemkul at outerbanks.umaryland.edu | (410) 706-7441
>> http://mackerell.umaryland.edu/~jalemkul
>>
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>
>
>

-- 
==================================================

Justin A. Lemkul, Ph.D.
Ruth L. Kirschstein NRSA Postdoctoral Fellow

Department of Pharmaceutical Sciences
School of Pharmacy
Health Sciences Facility II, Room 629
University of Maryland, Baltimore
20 Penn St.
Baltimore, MD 21201

jalemkul at outerbanks.umaryland.edu | (410) 706-7441
http://mackerell.umaryland.edu/~jalemkul

==================================================


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