[gmx-users] Re: T->A mutation for a dimer protein

[Lishan Yao]

Dear Chris and Mark,
    Thank you both for the response. I did the simulation already and Gromacs only gives me the total dH/dl. The two mutated sites are more than 20A alway from each other which makes it safe to assume that the interaction between the two sites is small. If I can extract dH/dl for each site, I could get a resonable error estimation of my calculation. Furthermore, if this is reliable I will do different mutations in two monomers (as long as they are away from each other) so that I can save my computational time by 50%. I guess this will involve some code change.

Best,
Lishan



> From: chris.neale at utoronto.ca
> Subject: [gmx-users] T->A mutation for a dimer protein
> To: gmx-users at gromacs.org
> Message-ID: <20110622210442.mmbm5utlww08k40w at webmail.utoronto.ca>
> Content-Type: text/plain; charset=ISO-8859-1; DelSp="Yes";
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> 
> Dear Lishan:
> 
> First, it would be great to see some evidence that you have tried to  
> do this yourself before posting. Your "I think" makes it a possible  
> waste of time for us to suggest a resolution to a problem that may or  
> may not exist.
> 
> Second, if indeed it is a problem, perhaps you could use two identical  
> topologies with different molecule names and treat them separately.
> 
> Chris
> 
Message: 3
Date: Thu, 23 Jun 2011 11:40:20 +1000
From: Mark Abraham <Mark.Abraham at anu.edu.au>
Subject: Re: [gmx-users] T->A mutation for a dimer protein
To: Discussion list for GROMACS users <gmx-users at gromacs.org>
Message-ID: <4E029984.9040405 at anu.edu.au>
Content-Type: text/plain; charset="iso-8859-1"

On 23/06/2011 9:48 AM, yaolisha at msu.edu wrote:
>
> Hi All,
> I have a protein dimer and I want to calculate a T to A mutation free 
> energy change using TI method. Since it is a dimer, it is very 
> convenient (and advantageous) to mutate the T in both monomer 
> simultaneously. Gromacs will write out dH/dl sum for the two mutations 
> together, I think. My question is how can I change Gromacs so than 
> dH/dl for T->A mutation in each monomer is written out separately?
>

You can't, because both have contributions from all the interactions. If 
your method is sound, i.e. both mutations can take place without 
affecting the other (big assumption IMO), surely you can just halve 
dH/dl from the combined mutation to get the single-mutation dH/dl?

Mark