Re: FEP tutorial graph question

From: Christopher Hartshorn (
Date: Wed Apr 29 2009 - 19:52:28 CDT

Yes, sorry I forgot to add that and I had told myself to do so before
hand. I am using the latest 2.7b1 executable mainly because I was
under the impression that for what I wished to do (double-annhilation
of a very small antimicrobial peptide), that it would be my best
option (before the beta was released as an executable I had been using
a CVS version from last December).

Thank you


On Apr 29, 2009, at 2:17 PM, Chris Harrison wrote:

> Chris,
> Before I answer your many questions, which version of NAMD are you
> using? If the cvs version, on what date was it checked out or
> downloaded? There are significant differences between the FEP
> implementations depending upon the NAMD version.
> C.
> --
> Chris Harrison, Ph.D.
> Theoretical and Computational Biophysics Group
> NIH Resource for Macromolecular Modeling and Bioinformatics
> Beckman Institute for Advanced Science and Technology
> University of Illinois, 405 N. Mathews Ave., Urbana, IL 61801
> Voice: 217-244-1733
> Fax: 217-244-6078
> On Wed, Apr 29, 2009 at 3:35 PM, Christopher Hartshorn <
> > wrote:
> Hello all. I am having problems figuring out why my plot of dG vs.
> lambda looks nothing like the plot in the FEP tutorial writeup. I
> understand that I will not necessarily get the same ddG because of
> various issues, but what I get is nothing like anything I have seen
> (including all published sources). I have followed the tutorial to
> the letter (minimize, equilibrate, and FEP with 100K iterations/
> lambda step) with the tyr2ala part, but when I plot up the results
> they look completely different (as in they curve up then down then
> up and then down again not the smooth curve I see in most). I have
> a small jpeg (73KB) of the graph I can send if need be. I generate
> these plots by using the .fepout files lines that contain:
> #Free energy change for lambda window [ 0 1e-05 ] is 0.0253223 ; net
> change until now is 0.0253223
> And then simply plotting the step versus the net change until now
> (e.g. 1e-05 vs. 0.0253223 in the above example). Am I doing this
> wrong? Plotting up the wrong data? I began doing this because I
> was seeing the same results when I plotted up some FEP calculations
> that I am doing on systems of mine and wanted to see if I could even
> get the tutorial done correctly (which I clearly can not, meaning I
> must be missing some point here because none of my graphs of dG vs
> lambda have the smooth curves I have seen every where else).
> Also, as a side note I have read of people who do an averaging of
> both directions to get better results. But I am not sure if they
> mean forward direction= (going from 0 to 1) and then 1 to 0 for
> reverse direction or if they mean that forward=fading out (beta
> column=-1) interaction of molecule of interest from 0 to 1 and
> reverse=fading in (beta column=1) molecule of interest from 0 to 1
> (although, I guess those are probably the same things my question is
> with respect to NAMD and which is the better way, if any, in
> practice). Is this averaging actually better then going in the
> "more" correct direction to begin with (e.g. the direction of lower
> entropy)?
> Finally, and I will stop here, I thought I had read of people
> putting restraints on (or even fixing) the molecule that is being
> faded in/out for the FEP calculation. Is this normal practice?
> Thank you very much in advance.
> Chris Hartshorn

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