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

[Mark Abraham]

On 23/06/2011 12:22 PM, Lishan Yao wrote:
> Dear Chris and Mark,
>      Thank you both for the response. I did the simulation already and Gromacs only gives me the total dH/dl.

So what's wrong with dividing by two, like I suggested last time? You've 
got two events and you assert that they're independent, so the 
statistics should be easy.

>   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.

To which mutation would you assign the energy contribution of the atoms 
around half way between them?

Mark

> 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";
>> format="flowed"
>>
>> 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