I tend to agree- to my knowledge, this has never been carried out to
reasonable convergence in the literature for a peptide this size in
explicit water. By "convergence" I mean showing that very similar results
are obtained regardless of starting conformation. That's stricter than some
reports where it is claimed that the populations are no longer changing,
which I find not as satisfying as it should be (in my opinion). Niel is
right, if you want to just do a conformational search, this could be fine,
but if you're looking for the populations themselves to be reliable, it's
still perhaps intractable.
I'm not sure which comments of mine on implicit solvent you reference. our
GB models have gotten better, and with igb=8 you might find that you get
what you need. Look at our article on it and see if it's what you need,
though the test systems are much smaller than what you're proposing.
1. Nguyen, H., Roe, D. and Simmerling, C., “Improved Generalized Born
Solvent Model Parameters for Protein Simulations”, J. Chem. Theory &
Comput., 9, 2020–2034 (2013) DOI: 10.1021/ct3010485
On Tue, Sep 10, 2013 at 10:01 AM, Niel Henriksen <shireham.gmail.com> wrote:
> Francesco,
>
> More than 200 replicas could be a major challenge, especially with explicit
> solvent. If you hope to find some plausible folded conformations, it might
> work (i don't know that you need to go to 600K though). If you hope to
> converge the entire ensemble, you might want to avoid this particular
> route. I had trouble converging a tetranucleotide in explicit water with
> ~4 microseconds/replica of simulation (24 replicas).
> http://www.ncbi.nlm.nih.gov/pubmed/23477537
>
> --Niel
>
>
> On Tue, Sep 10, 2013 at 6:45 AM, Francesco Pietra <chiendarret.gmail.com
> >wrote:
>
> > >Assuming that I am interpreting your question correctly,
> >
> > Yes, and the answer is very useful: I can assume a larger delta T than
> the
> > 0.8K I reported. Provided that I will be able to calculate the exchange
> > frequency (so far unclear to me how; I can just change the number of
> > steps/run, I used 100, if increased to 1000 there is no more any
> exchange).
> >
> > At any event, are >200 replicas (as needed with my system for 314-600K) a
> > reasonable prospect or one that is destined to result as technically
> > unfeasible? The literature is abundant of variants on small peptides.
> >
> > Finally, is exhaustive MD equilibration an absolute need or it can just
> > help? So far I have not insisted in the equilibration at 314K
> (rmsd/frame
> > is still raising because - I suppose - of the flexibility of the portion
> to
> > model: clearly there are low energy barriers)
> >
> > Thanks
> >
> > francesco pietra
> >
> >
> > On Tue, Sep 10, 2013 at 1:12 PM, Jason Swails <jason.swails.gmail.com
> > >wrote:
> >
> > > On Tue, Sep 10, 2013 at 3:38 AM, Francesco Pietra <
> chiendarret.gmail.com
> > > >wrote:
> > >
> > > > Hello:
> > > > I am progressing toward a major task of carrying out a pure T-remd
> > > > (parallel tempering) with a 34aa peptide in explicit water for a
> > 314-600K
> > > > range. After C. Simmerling reports about implic media, I did not
> > attempt
> > > > any simulation under implicit media.
> > > >
> > > > I started with 8 replicas and geom progressing temp, noticing, for
> the
> > > > 314-320K range, full exchange is obtained. deltaT is 0.8K.
> > > >
> > > > On increasing the nr of replicas and delta T on the above basis, thus
> > 16
> > > > replicas for 314-326K, the exchange is no more so good. That is, the
> > > > highest and the lowest temp do not exchange with one another
> directly.
> > > >
> > > > My question is, do, for example, exchange of 16 with 15 only, and
> > > exchange
> > > > of 14 with 15, compensate? In other words, do "local exchanges"
> > > propagate?
> > > >
> > > > In this affair, I restrained the dihedrals for a two (starting) alpha
> > > > helical turns, which are well defined by X-ray diffraction. The rest
> of
> > > the
> > > > peptide does not clearly diffract at 100K, and I am attempting to
> > > simulate
> > > > how the conformation, or prevailing cluster of conformations, should
> > be.
> > > I
> > > > did not apply any other restraint to this undefined part. Should the
> > > > chirality at the peptide bond be imposed even if the prevailing
> > > > conformation is unknown?
> > > >
> > > > Thanks so much for advice
> > > >
> > >
> > > Assuming that I am interpreting your question correctly, there is no
> need
> > > to achieve exchanges between the first and last temperature replica.
> In
> > > fact, if you are achieving exchanges between those two a high
> percentage
> > of
> > > the time, then all of the replicas in between are unnecessary :). As
> > long
> > > as adjacent replicas exchange frequently enough (about 20% of the time
> is
> > > good in my experience), then you will get good enough mixing in state
> > space
> > > to make efficient use of REMD. (Replicas will be able to diffuse
> through
> > > state space from the lowest temperature to the highest _through_ the
> > > intermediate temperatures).
> > >
> > > The following website will give you a good set of starting temperatures
> > > between two replicas: http://folding.bmc.uu.se/remd/ (the NPT results
> > are
> > > good enough for the NVT REMD that Amber runs). It may be worth
> running a
> > > quick simulation to verify that all exchange rates are approximately
> what
> > > you want them to be before starting major production.
> > >
> > > HTH,
> > > Jason
> > >
> > > --
> > > Jason M. Swails
> > > BioMaPS,
> > > Rutgers University
> > > Postdoctoral Researcher
> > > _______________________________________________
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> > > AMBER.ambermd.org
> > > http://lists.ambermd.org/mailman/listinfo/amber
> > >
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> >
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Received on Tue Sep 10 2013 - 07:30:03 PDT
