[gmx-users] Obtaining PMF for change in domain position

Justin Lemkul jalemkul at vt.edu
Mon Dec 29 16:29:32 CET 2014

On 12/29/14 6:57 AM, Abhi Acharya wrote:
> Hello GROMACS Users,
> This is a problem I am facing for the first time. Kindly guide be to the
> best options.
> I have a protein which has two large domains connected by a flexible linker
> peptide (~10 aa). The two domains seem to interact with each other and have
> been crystallized in three different conformations. I want to calculate the
> change in binding energy of the two domains wrt change in their relative
> position, i.e. keeping position of one domain constant what is change in
> binding energy as the other domain moves from conformation 1, through
> conformation 2 to finally, conformation 3. What is the best way to do so?

You need to describe what these three conformations are.  Do they involve 
rotations of the domains with respect to one another, or is it a simple linear 
distance that varies?

> At first, I considered using umbrella sampling to address the problem. Here
> too, I was not sure how to write a pull code for such a complex reaction
> coordinate. Also, even if I can generate the conformations, what would be
> the ideal number of windows that would be needed to correctly generate a
> PMF ? My feeling is it would be a large number, but again it just a guess.
> Is there is a better way than this?

Hard to know a priori.  You may need some trial and error here, but with 
umbrella sampling it's trivial to just go back and add windows, since the 
simulations are still all independent of one another.



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


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