[gmx-users] Which/What is the adequate overlap using g_BAR

Justin Lemkul jalemkul at vt.edu
Tue Jul 9 13:17:23 CEST 2013

On 7/8/13 4:27 PM, mike.nemec at stud.uni-due.de wrote:
> Dear Gromacs People,
> I want to calculate free energy differences between two states A and B
> using g_BAR.
> For this I read many papers concerning the overlap between neighboring
> sample windows (Delta H) but I am still wondering about the following issue:
> I know, that there has to be an adequate overlap to get accurate free
> energy differences, but I am not sure, which neighboring sample
> distributions have to overlap in the gromacs nomenclature.
> Do the neighboring distributions N(Delta H(lambda=0.05) | lambda=0) AND
> N(Delta H(lambda=0) | lambda=0.05) have to overlap? Or shall there be an
> overlap between neighboring distributions calculated from the left side
> N(Delta H(lambda=0.05) | lambda=0) ; N(Delta H(lambda=0.10) |
> lambda=0.05) ; N(Delta H(lambda=0.15) | lambda=0.10) ...
> and then neighboring from the right side
> N(Delta H(lambda=0) | lambda=0.05) ; N(Delta H(lambda=0.05) |
> lambda=0.10) ; N(Delta H(lambda=0.10) | lambda=0.15) ... ?
> I am puzzled, because if one takes a hypothetic stepsize of "1", then
> one only gets two distributions
> N(Delta H(lambda=1) | lambda=0) AND N(Delta H(lambda=0) | lambda=1)
> which then should overlap to get a right free energy difference
> estimation. Am I right?

Perhaps I'm a bit confused on how you're presenting the question.  Are you 
asking about "forward" and "reverse" transformations giving an equivalent 
result?  Keep in mind that there is no such directionality in these types of 
transformations, as long as you're not using a slow-growth method.  Otherwise, I 
don't see how one can have left-handed overlap but not right-handed overlap in 
adjacent distributions.  Either the neighboring lambda windows overlap or don't.

> So, concluding this, the last two cases should be right, but refering to the
> "mailing-list-question" of Fabian Casteblanco
> http://gromacs.5086.x6.nabble.com/Free-energy-sampling-using-G-bar-td4455419.html#a4455420
> Justin Lemkul replies, that "the histograms look fine [...]. Lots of
> overlap.", which would result, that all the "left-side" and all the
> "right-side" neighbor distributions have to overlap, I think
> Depending on your answer, can you please explain, why thedistributions
> of your answer have to overlap, and not the others?
> For this case I calculated the free energy difference with g_BAR of one
> tripeptide Valine-Leucine-Valine where thepartial charges of the Leucine
> are turned to "0" from state A to B in steps of "0.02" (see attachement,
> representative 4 neighboring distributions). In the case, that all the
> "left side calculated" and all the "right side calculated" neighbor
> distributions have to overlap, the overlap in the attached file is great,
> isn't it?
> But is that really the correct overlap?

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Justin A. Lemkul, Ph.D.
Postdoctoral Associate

Department of Pharmaceutical Sciences
School of Pharmacy
Health Sciences Facility II, Room 601
University of Maryland, Baltimore
20 Penn St.
Baltimore, MD 21201

jalemkul at outerbanks.umaryland.edu | (410) 706-7441


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