[gmx-developers] site specific dH/dl

[Shirts, Michael (mrs5pt)]

> Strictly speaking it is not well posed.
> But in practice this might often be a useful thing to do.

I think it's probably better to turn an ill-posed question into a well-posed
question before going much further in trying to solve it!

> But I have worked on coupling small solutes into a polymer matrix,
> which often needs to be large. In that case be able to independently
> couple several molecules would be very useful.

So, I think what one wants to describe coupling is (ddG_coupling) =
(dG_both)-(dG_1 + dG_2), where the three calculations are all performed
independently.

> If the system here is a homo-dimer, you don't need the two numbers,
> you can simply divide the total by two. But if they would couple,
> this might not be correct.

With even a homodimer, there is still coupling -- but there you can compute
(ddG_coupling) = (dG_both)-(2*dG_1), with only two calculations.

Best,
~~~~~~~~~~~~
Michael Shirts
Assistant Professor
Department of Chemical Engineering
University of Virginia
michael.shirts at virginia.edu
(434)-243-1821


> If the system here is a homo-dimer, you don't need the two numbers,
> you can simply divide the total by two. But if they would couple,
> this might not be correct.
> 
> But I have worked on coupling small solutes into a polymer matrix,
> which often needs to be large. In that case be able to independently
> couple several molecules would be very useful.
> 
> Berk
> 
> On 06/23/2011 01:37 PM, Shirts, Michael (mrs5pt) wrote:
>> I'm not sure the question is even well-posed.  If you change two things at
>> once, you cannot decompose what the free energy is into two spatially
>> separate parts.  You can compute the free energy of the first mutation, then
>> performing the second mutation given that the first mutation exists.  Both
>> free energies will be different (perhaps not very different if the locations
>> as well separated) than if you tried to do both at once.
>> 
>> Best,
>> ~~~~~~~~~~~~
>> Michael Shirts
>> Assistant Professor
>> Department of Chemical Engineering
>> University of Virginia
>> michael.shirts at virginia.edu
>> (434)-243-1821
>> 
>> 
>>> From: Berk Hess<hess at cbr.su.se>
>>> Reply-To: Discussion list for GROMACS
>>> development<gmx-developers at gromacs.org>
>>> Date: Thu, 23 Jun 2011 11:26:49 +0200
>>> To: Discussion list for GROMACS development<gmx-developers at gromacs.org>
>>> Subject: Re: [gmx-developers] site specific dH/dl
>>> 
>>> Hi,
>>> 
>>> This is impossible with the current code.
>>> It would not be too hard to this with the Bennett's acceptance ratio code,
>>> but that requires the code as well as the analysis tools to support multiple
>>> decoupling groups (which could be done through energy groups).
>>> This is mainly a bookkeeping issue, which would also require a change
>>> of file formats.
>>> 
>>> Berk
>>> 
>>> On 06/23/2011 05:47 AM, Lishan Yao wrote:
>>>> Hi:
>>>> 
>>>> I did a MD TI simulation for a T->   A mutation in a protein dimer. The
>>>> mutations were done in both sites simultaneously. My question is how can I
>>>> extract dH/dl for each T->A site. Gromacs gives the total dH/dl. Which part
>>>> of the code should I change?
>>>> 
>>>> Best,
>>>> Lishan
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