HI Neil,
Thanks for sharing your paper.
Best
Sudipta
On Thu, Mar 14, 2013 at 9:39 PM, Niel Henriksen <niel.henriksen.utah.edu>wrote:
> Sudipta,
>
> We have run quite a few REMD simulations in explicit solvent.
> They are computationally expensive, but we do it because our
> RNA simulations perform badly with implicit solvent.
>
> We just published a paper which discusses some of the hurdles
> with this approach, specifically convergence. If you want to do
> explicit solvent REMD, take a look:
>
> http://pubs.acs.org/doi/abs/10.1021/jp400530e
>
> Good luck,
> --Niel
> ________________________________________
> From: sudipta [sudipta.mml.gmail.com]
> Sent: Thursday, March 14, 2013 5:51 PM
> To: AMBER Mailing List
> Subject: Re: [AMBER] REMD simulation
>
> Hi Jason,
>
> Thank you very much for the answer in detail. I truly appreciate your
> comments.
>
> Best
> Sudipta
>
> On Thu, Mar 14, 2013 at 7:43 PM, Jason Swails <jason.swails.gmail.com
> >wrote:
>
> > 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
> > _______________________________________________
> > AMBER mailing list
> > AMBER.ambermd.org
> > http://lists.ambermd.org/mailman/listinfo/amber
> >
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Received on Fri Mar 15 2013 - 09:30:04 PDT
