[gmx-users] Doubt about Free Energy Calculations using g_bar

Sun Jun 11 23:48:13 CEST 2017

Dear Mark,

I humbly disagree that the observations could not provide an insight into the physical systems because a previous the work provides a reasonable proof: "Theory and normal-mode analysis of change in protein vibrational dynamics on ligand binding", DOI: 10.1021/jp909677p

I wish to extend the said work and it speaks about the generation of a hypothetical “intermediate” state, without the ligand force field but with a structure resembling to that of the Bound complex state. It reveals that during the binding occurs from intermediate to the bound state, the vibrational entropies of both the protein and the ligand decrease, thereby predicting the physical state properties.

Even if the hypothesis is not true, I wish to proceed the required procedure and it would be helpful if you could provide any valuable revelation of doing the same in gromacs.

Best Regards,

Bhagyesh

----- Original Message -----
From: "Mark Abraham" <mark.j.abraham at gmail.com>
To: gmx-users at gromacs.org
Sent: Monday, June 12, 2017 2:43:53 AM
Subject: Re: [gmx-users] Doubt about Free Energy Calculations using g_bar

Hi,

On Sun, Jun 11, 2017 at 10:39 PM Varvdekar Bhagyesh Rajendra <
bhagyesh.varvdekar at research.iiit.ac.in> wrote:

> Dear Mark,
>
> Unless I'm mistaken, even though they are non-physical states and do not
> exist in reality, they have the required modification in the actual
> physical state (precisely, the non bonded interaction between protein and
> ligand) that I actually need and I wish to use the same and do Normal mode
> calculations to study the effect of the said perturbation at each lambda
> from 0 to 1.
>
> I would appreciate any suggestions to undertake the above quest.
>

I expect that the numbers you seek will be computed. But you're also going
to scale down e.g. the ligand-solute interactions, and IMO it's unlikely
you'll observe anything that you can claim is insight into the physical
systems.

Mark

> Best Regards,
>
> Bhagyesh
>
> ----- Original Message -----
> From: "Mark Abraham" <mark.j.abraham at gmail.com>
> To: gmx-users at gromacs.org
> Sent: Sunday, June 11, 2017 9:22:51 PM
> Subject: Re: [gmx-users] Doubt about Free Energy Calculations using g_bar
>
> Hi,
>
> To what end? These are non-physical states.
>
> Mark
>
> On Sun, 11 Jun 2017 16:28 Varvdekar Bhagyesh Rajendra <
> bhagyesh.varvdekar at research.iiit.ac.in> wrote:
>
> > Dear Justin,
> >
> > Thank you for the valuable insight.
> >
> > While on the same subject, can you give any comments on the possibility
> of
> > using the same Free energy code in Gromacs to scale the non bonded
> > interactions between protein & ligand while simultaneously doing Normal
> > Mode analysis on the scaled interaction conformation to study the effect
> of
> > the scaled interactions.
> >
> > If its not plausible in Gromacs, can you suggest any other software.
> >
> > Best Regards,
> >
> > Bhagyesh
> >
> > ----- Original Message -----
> > From: "Justin Lemkul" <jalemkul at vt.edu>
> > To: gmx-users at gromacs.org
> > Sent: Sunday, June 11, 2017 7:01:26 AM
> > Subject: Re: [gmx-users] Doubt about Free Energy Calculations using g_bar
> >
> > On 6/10/17 6:15 AM, Varvdekar Bhagyesh Rajendra wrote:
> > > Dear Justin,
> > >
> > > Just so we are on the same page, this means that if I don't touch the
> > topology file and use the following mdp snippet, charges *are present* in
> > the topology file for the ligand group and they are automatically set to
> > zero while turning on vdW interactions (from 0 to 1) right ? Hence, there
> > is no need to manually set charges to zero (The old style of doing the
> > calculations), right?.
> > >
> >
> > Yes.  You can easily confirm this using energygrps between your
> transformed
> > molecule and the rest of the system.  Coul-SR should be zero.
> >
> > > Then the charges too, are turned off from 0 to 1? (1 state being the
> > actual charges present in the topology file).
> > >
> >
> > Charges are turned *on* if they are defined as off in the A-state
> > (lambda=0) and
> > on in the B-state (lambda=1).
> >
> > -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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