hi Francesco,
If you can access to GPU cluster, you might want to try implicit
solvent simulation (like igb=8) first. Instead of running expensive
REMD, you can run multiple MD simulations (with different ig number or
different starting structures). With GPU cluster and igb8, you might
get about 500 ns/day.
Hai
On Tue, Sep 10, 2013 at 11:22 AM, Francesco Pietra
<chiendarret.gmail.com> wrote:
>
> I was at your earlier papers. May I ask for a pdf of the 2013 cited
> article? At our poor academy we do not subscribe that journal <
> francesco.pietra.accademialucchese.it>.
>
> My aim was to hopefully arrive at a major cluster of conformations, if
> any. It would be an improvement anyway on lack of useful diffraction by
> this part of the protein (Following Modeller integration of lacking
> portions, I have detached a portion of the six X-ray diffr indescribable
> portions, planning to superimpose the T-remd-resulting cluster through the
> few well described helical turns and delete the original). NMR - in my
> hands - proved unable to treat the case. So, theory was left.
>
> It deals of a transmembrane protein, with the portions to model just
> emerging from the bilayer. Nonetheless, I could also try implicit.
>
> Thanks a lot
> francesco pietra
>
>
> On Tue, Sep 10, 2013 at 4:13 PM, Carlos Simmerling <
> carlos.simmerling.gmail.com> wrote:
>
> > 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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Received on Tue Sep 10 2013 - 15:30:02 PDT
