On Thu, Mar 14, 2013 at 7:07 PM, sudipta <sudipta.mml.gmail.com> wrote:
> Hi Niel,
>
> Thank you very much for your reply. Yeah, I noticed that most of the people
> had used NVT instead of NPT. Nobody has not put any straightforward reason
> for choosing NVT over NPT.
Convenience and simplicity. The exchange probability is currently
calculated from basically a ratio of Boltzmann probabilities between the
two states in adjacent replicas. Boltzmann probabilities are valid for
NVT, only. To support NPT with REMD, a PV term needs to be added, I think.
> However, is the simulation of protein system at
> high temperature in NVT ensemble reasonable? When we increase the
> temperature of such system then the protein molecule will be expanded and
> it looks for some space. However, NVT ensemble doesn't compromise any
> space. I am curious about this.
>
When fluctuations are not important, all ensembles are effectively
identical. It is only when these fluctuations begin to become large (at,
for instance, phase transitions), that you need to be careful about your
ensemble. However, the purpose of the high-temperature replicas is NOT to
see how the system behaves at that temperature. In fact, many T-REMD
simulations have replicas at temperatures over the boiling point of water
at 1 bar.
To properly model this behavior, you would naturally need to use NPT... but
you don't want to model the behavior of boiling proteins (if you did, then
a force field parametrized at 300K is _not_ the way to go). The only
purpose of using high-temperature replicas is to generate a series of
structures that 'might' be relevant at a lower temperature that are hard to
reach there due to large barriers in phase space.
The fact that high-temperature replicas are nonsensical due to the force
field not being validated at such temperatures as well as the issues you
raise due to our choice of ensemble are actually irrelevant. Because the
exchange probability obeys detailed balance, you are assured that your
low-temperature replicas are thermodynamically correct. The
high-temperature replicas are used only to enhance sampling and serve
little use after the simulation is over (you can use them for some stuff,
like reweighting, but are often just discarded).
In fact, if you ran NPT, then you would actually _hurt_ your exchange
success rate if you came anywhere close to the boiling point of water,
since the volume would expand too much. So IMO, NVT is the better choice
for most REMD simulations.
Another issue is use of explicit solvent. Most of REMD study has been
> performed in implicit solvent environment. Is there any inherent reason
> behind this except computational cost.
>
Computational cost is the only reason. But the computational cost
increases for two reasons. First, more particles means slower simulations,
and the viscosity of water molecules hinders conformational sampling in
explicit solvent compared to implicit solvent -- so you need longer
simulations that run slower.
Even worse with REMD, though, is that the width of your potential energy
distribution scales as 1/sqrt(N) where N is the # of particles. With
explicit solvent (or any large system), the number of particles becomes
large, so the potential energy distributions become narrow. Since these
distributions must overlap in order for REMD to be effective, you need to
place replicas much closer together. Therefore, in order to span the same
temperature range in explicit solvent, you often need many, many more
replicas.
That is why T-REMD simulations are typically (although not always) run with
implicit solvent unless the system size is rather small to begin with.
(e.g., alanine dipeptide)
HTH,
Jason
--
Jason M. Swails
Quantum Theory Project,
University of Florida
Ph.D. Candidate
352-392-4032
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Received on Thu Mar 14 2013 - 17:00:04 PDT
