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From: Jason Swails <jason.swails.gmail.com>

Date: Thu, 13 Aug 2015 08:43:41 -0400

On Thu, 2015-08-13 at 14:58 +0800, whb wrote:

*> Hi all：
*

*>
*

*> I have a question about the method of pH-REMD. I’ve read the paper
*

*> published in JCTC(J. Chem. Theory Comput., 2014, 10 (3), pp 1341–1352).
*

*>
*

*> It said that the probability of accepting these replica exchange attempts,
*

*> given by eq 3, depends only on the difference in the number of titrating
*

*> protons present in each replica and their respective difference in pH
*

*>
*

*>
*

*>
*

*> I think that it contains an assumption that the residue in lower pH can be
*

*> more protonated. But I think that pka of the residue depends the environment
*

*> where the residue exists in the protein. And when the proteins structure has
*

*> changed severely in lower pH , the residue may have another pH in that
*

*> situation. And this situation may contradict with the assumption the theory
*

*> contains.
*

There are indeed a lot of assumptions made in any MD simulation --

pH-REMD included. However, the *replica* exchange acceptance

probability that you refer to is derived directly by solving the

detailed balance equation of the probability distribution functions for

the semi-grand canonical ensemble. Therefore, this is one of the few

aspects of the simulation that is, in fact, *not* an approximation and

is exact.

The effect of the protein environment is accounted for by the

protonation state change attempts *within* a replica (keep in mind there

are two Monte Carlo change attempts being made -- one between

protonation states and the other between replicas). I present an

abbreviated derivation of this equation on my Wiki:

http://jswails.wikidot.com/ph-remd#toc16 and there are also more

detailed explanations about replica exchange in general as well as the

basic theory underlying constant pH simulations in my dissertation:

http://jswails.wdfiles.com/local--files/about/jms_Dissertation.pdf

HTH,

Jason

Date: Thu, 13 Aug 2015 08:43:41 -0400

On Thu, 2015-08-13 at 14:58 +0800, whb wrote:

There are indeed a lot of assumptions made in any MD simulation --

pH-REMD included. However, the *replica* exchange acceptance

probability that you refer to is derived directly by solving the

detailed balance equation of the probability distribution functions for

the semi-grand canonical ensemble. Therefore, this is one of the few

aspects of the simulation that is, in fact, *not* an approximation and

is exact.

The effect of the protein environment is accounted for by the

protonation state change attempts *within* a replica (keep in mind there

are two Monte Carlo change attempts being made -- one between

protonation states and the other between replicas). I present an

abbreviated derivation of this equation on my Wiki:

http://jswails.wikidot.com/ph-remd#toc16 and there are also more

detailed explanations about replica exchange in general as well as the

basic theory underlying constant pH simulations in my dissertation:

http://jswails.wdfiles.com/local--files/about/jms_Dissertation.pdf

HTH,

Jason

-- Jason M. Swails BioMaPS, Rutgers University Postdoctoral Researcher _______________________________________________ AMBER mailing list AMBER.ambermd.org http://lists.ambermd.org/mailman/listinfo/amberReceived on Thu Aug 13 2015 - 06:00:03 PDT

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