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

[Sneha Vishwanath]

Dear Rahul and Justin

Thanks for the suggestion, I will check the parameterisation once more.

Regards
Sneha

On Sat, Jul 22, 2017 at 7:05 AM, RAHUL SURESH <drrahulsuresh at gmail.com>
wrote:

> 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*
> --
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