Re: [AMBER] NPT equilibration at constant pH with protonation states allowed to change

From: Eric Lang <>
Date: Fri, 11 Nov 2016 21:18:50 +0000

Dear Jason,

Thanks a lot for your reply.
Sorry, I did not make myself clear: I know that I cannot run REMD in NPT a
that each replica needs to have exactly the same box size.

What I would like to do after minimisation and heating is to run a *single*
replica at pH 7 in NPT allowing the protonation states to change (so
effectively NPT CpHMD). This would be the equilibration run. I would
therefore end up with an equilibrated structure in which all the ionisable
residues won't be necessarily be protonated. I then want to use this
structure as a starting point for all the replicas for pH-REMD, which would
be run in NVT (so I would do the split at this stage after NPT
equilibration at constant pH).

What I would like to know is:
- Is it possible to run CpHMD (not pH-REMD) in NPT?
- Is it a problem to have, for each replica of the pH-REMD, a starting
structure that does not have all the protons (and is protonated according
to a given pH) or is there a risk that this will lead to a poor protonation
state sampling ?

Many thanks in advance,


On 11 November 2016 at 17:39, Jason Swails <> wrote:

> On Fri, Nov 11, 2016 at 12:31 PM, Eric Lang <>
> wrote:
>> Hello,
>> I want to run some explicit solvent pH-REMD simulations, and I just want
>> to
>> check if, after the heating phase, I can run a NPT equilibration at a
>> constant pH with the protonation states allowed to change.
> ​NpT + REMD in Amber is not supported for any kind of REMD. Furthermore,
> every replica *should* have exactly the same box size when doing REMD with
> PBC. This is because the exchange criteria does not incorporate
> volume/pressure contributions, as I believe would be required to correctly
> sample from the desired distribution.
> The proper procedure to use is to run a *single* replica until you get a
> stabilized and sensible density, then build each replica from that starting
> point using NVT the rest of the time.
> HTH,
> Jason
> --
> Jason M. Swails

Eric Lang
BrisSynBio Postdoctoral Research Associate Modelling
Centre for Computational Chemistry
School of Chemistry - University of Bristol
Bristol BS8 1TS - United Kingdom
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Received on Fri Nov 11 2016 - 13:30:02 PST
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