[gmx-users] ligand moving out during umbrella sampling

Sun May 21 17:09:51 CEST 2017

Beg your pardon, I have not ignored your comment entirely regarding using
specific residue COM. I just recently succeeded performing md_umbrella
simulation (using protein COM) on few configurations.
.
I have not used specific residues COM so far as because of some confusions
regrading defining it. The residue stretch is not continuous e.g. residue
6-10, 78-80, 56, 63, 35 are to be active site residue. I got no idea how to
define such discrete set of residues using make_ndx command.

On Sun, May 21, 2017 at 8:13 PM, Justin Lemkul <jalemkul at vt.edu> wrote:

>
>
> 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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> Gromacs Users mailing list
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-- 
Abhisek Mondal

*Senior Research Fellow*

*Structural Biology and Bioinformatics Division*
*CSIR-Indian Institute of Chemical Biology*

*Kolkata 700032*

*INDIA*