[gmx-users] protein -ligand complex dissociating during simulation

[Justin Lemkul]

On 7/21/17 10:56 AM, RAHUL SURESH wrote:
> It sounds like some internal dihedral problem. Request you, check on it.
> 

How did you deduce that?

Indeed, conformational sampling may be an issue, so one should check the 
internal geometries of the ligands, preservation of various interactions with 
the protein (H-bonding and other characteristic distances and angles, etc). 
Revisit your parametrization, if you used some black-box method without 
validation and/or refinement, you may just have a junk ligand topology.

-Justin

> On Fri, 21 Jul 2017 at 6:54 PM, Sneha Vishwanath <
> snehavishwanath09 at gmail.com> wrote:
> 
>> @ Justin: I have re-imaged  the trajectory with trjconv using and still the
>> ligand dissociates from one of the chain but remain bound with the other
>> chain.
>>
>> @ Gangotri: I am not sure how constraining the bond between protein might
>> help. Can you please elaborate if possible.
>>
>> Thanks in advance.
>>
>> Sneha
>>
>> On Fri, Jul 21, 2017 at 6:37 PM, Justin Lemkul <jalemkul at vt.edu> wrote:
>>
>>>
>>>
>>> On 7/21/17 8:56 AM, Sneha Vishwanath wrote:
>>>
>>>> Dear all
>>>>
>>>> I am simulating a dimeric protein, with each subunit bound to a small
>>>> molecule. During the simulation, one of the ligands is dissociating from
>>>> the chain and moving all around the chain while the same ligand remains
>>>> bound to the chain during simulation. Experiments show that the ligand
>>>> binds to both the subunit which is further supported by the experimental
>>>> structure of the protein-ligand complex (which I have used for the
>>>> simulation). The simulation is for 50 ns and it usually starts
>>>> dissociating
>>>> after 10 ns.
>>>>
>>>> Any thoughts on why could it be happening and how it can be
>> circumvented?
>>>> Any help would be useful.
>>>>
>>>>
>>> Are you sure this is not simply a PBC artifact?  Have you
>>> re-imaged/centered the trajectory appropriately with trjconv?
>>>
>>> -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

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