Re: FEP tutorial graph question

From: Chris Harrison (char_at_ks.uiuc.edu)
Date: Wed Apr 29 2009 - 16:17:07 CDT

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
char_at_ks.uiuc.edu                            Voice: 217-244-1733
http://www.ks.uiuc.edu/~char               Fax: 217-244-6078
On Wed, Apr 29, 2009 at 3:35 PM, Christopher Hartshorn
<cmhartshorn_at_wsu.edu>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
> #NEW FEP WINDOW: LAMBDA SET TO 1e-05 LAMBDA2 0.0001
>
> 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
>
> WSU
>
>

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