Re: FEP with fixed explicit environment?

From: Chris Harrison (char_at_ks.uiuc.edu)
Date: Thu Mar 12 2009 - 22:05:24 CDT

Sebastian,

Simple question first: Can NAMD do this?
Yes. There's nothing in the code that prevents it. Can't think of a reason NAMD wouldn't execute successfully.

Hard question: Should you do this?
During any alchemical perturbation there is the possibility that the environment dynamically responds by rearranging its conformation. If you can justify that any changes of the conformational ensemble that occur during a restrained R->A perturbation are not significantly different from conformational ensemble changes that occur during an unrestrained R->A perturbation, then you may be able to do this. So, the atoms beyond your 30 Ang radius would have to fullfill the criteria that the dynamics of those atoms you wish to restrain do not respond to the R->A perturbation and the unrestrained atoms' dynamical response(s) to the perturbation is not altered by the presence of the restrained atoms.

Please let me know how it goes. I'm interested to know if it works successfully {meaning a) no NAMD crashes & b) you get a correct/reasonable result}.

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
Sebastian Stolzenberg <s.stolzenberg_at_gmail.com> writes:
> Date: Thu, 12 Mar 2009 19:50:32 -0400
> From: Sebastian Stolzenberg <s.stolzenberg_at_gmail.com>
> To: namd-l_at_ks.uiuc.edu
> Subject: namd-l: FEP with fixed explicit environment?
> Return-Path: char_at_halifax.ks.uiuc.edu
> Message-ID: <49B99FC8.2080505_at_gmail.com>
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> 
> Dear Everybody,
>
> I have an equilibrated NPT structure of a protein in explicit  
> lipid/solvent with periodic boundary conditions. Let's assume I do a  
> mutation R105A with dual-topology FEP. Certainly, I will also need to  
> transform a bulk water molecule (WAT) into a sodium (SOD) to keep the  
> net charge=0. To get the final free energy difference, I will subtract  
> delta_G(WAT->SOD) that I get from a separate run.
>
> The system is large, I was thinking about fixing all atoms of the system  
> except for the ones around ~30A of the R105A mutation and the WAT->SOD  
> transformation. (Of course, I will not have a fixation boundary crossing  
> covalent bonds that leads e.g. to RATTLE constraint violations).
>
> Is this feasible with NAMD-FEP? Any troubles with periodic boundary  
> conditions? I know that all could be locally done with implicit  
> lipid/solvent in CHARMM, which I would like to avoid for now.
>
> Thanks so much,
> Sebastian
>

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