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

[RAHUL SURESH]

On Sat, 22 Jul 2017 at 2:47 AM, Justin Lemkul <jalemkul at vt.edu> wrote:

>
>
> 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?


Dear Justin

I faced the similar kind of problem. Visualisation Of my trajectory helped
me a lot in solving this issue. I had to reparameterize the topology of
ligand to overcome this error.
Thank you

>
>
> 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
>
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-- 
*Regards,*
*Rahul Suresh*
*Research Scholar*
*Bharathiar University*
*Coimbatore*