Hii;
Hope for a fast and effective longer nano second simulation with Amber 14.
But I am more interested in setting a bench mark approach not a controversy
such as multiple vs continuous . Thanks all for very valuable discussions
and points. Thank you all so much.
On Mon, Mar 17, 2014 at 12:57 PM, filip fratev <filipfratev.yahoo.com>wrote:
> Hi Soumendranath,
>
> >Say for example in case of HIV protease a flap opening and closing occurs
> >after 50ns continuous MD. But if we adapt a multiple MD approach say for
> >example 5*10 or 10*5 or whatever then it will never show a biological
> >movement in longer time scale as in multiple MDs all sub MDs are
> >independent.
>
> Most of phenomenas that we usually study is in this range, thus thats way
> 5-8x100ns simulations with Amber 12 is the ideal choice for me. Just one
> 100ns will not be sufficient enough. With the power of Amber 14 we might
> extend the runs up to 200ns (the GPU version). Indeed a agree with you that
> a lot of events are beyond this range and in this case it is better just to
> not try to describe them with short simulation times.
>
>
> Regards,
> Filip
>
>
>
>
>
>
> On Monday, March 17, 2014 8:40 AM, Soumendranath Bhakat <
> bhakatsoumendranath.gmail.com> wrote:
>
> Dear Filip and Amberists;
>
> My opinion on this matter is as follows
> 1. Whenever we are going for a multiple MD e.g 5*100 or 100*5 we will never
> going to explore an event happening in a longer nano second timeframe.
> Say for example in case of HIV protease a flap opening and closing occurs
> after 50ns continuous MD. But if we adapt a multiple MD approach say for
> example 5*10 or 10*5 or whatever then it will never show a biological
> movement in longer time scale as in multiple MDs all sub MDs are
> independent. Phenomenas such as flap opening closing, etc. will never
> possible in multiple MD. Whereas in long continuous MD we can monitor
> certain very interesting biological events in very longer timescale.
> 2. I agree to the fact that multiple MD with more sampling points such as
> 5ns*10 will probably leads to a conclusive MMGBSA/MMPBSA scores rather than
> a long continuous MD.
>
> Lets hope that we might put a solid article with substantial evidence to
> end this story of continuous vs Multiple md.
> For me to understand dynamic behaviour of biological system always opted
> for continuous MD but for binding free energy calculation always opt for
> multiple MD approach.
> Cheers!!
>
>
> On Sat, Mar 15, 2014 at 4:23 AM, Bill Ross <ross.cgl.ucsf.edu> wrote:
>
> > A tool I am wont to recommend is low-temperature vacuum dynamics - you
> > can simulate a long time to get a feel for the range of movement of
> > your system, possibly cherry-picking representative frames to solvate
> > and run in parallel.
> >
> > Bill
> >
> > Brian Radak <radak004.umn.edu> wrote:
> >
> > > Back during my graduate preliminary exams I recall being (somewhat)
> > gently
> > > reminded that the validity of (nearly?) all statistical mechanical
> > > estimators in use in MD analysis are predicated on the *assumption* of
> > > ergodicity. That is, that the trajectory at hand is in fact really
> really
> > > long and has therefore visited all *relevant *regions of phase space.
> > >
> > > Now I would argue that this depends on how one defines relevant and
> that
> > > this is the great advantage/disadvantage of simulations in general, the
> > > complete control one has of defining the system/problem. The validity
> of
> > > this definition will probably reduce to physical arguments based on
> > > intuition and empirical knowledge of the problem at hand. Therefore, as
> > > Carlos pointed out, which tools are appropriate and which compromises
> are
> > > best is likely to always be a case by case challenge.
> > >
> > > Regards,
> > > Brian
> > >
> > >
> > > On Wed, Mar 5, 2014 at 9:46 AM, Carlos Simmerling <
> > > carlos.simmerling.gmail.com> wrote:
> > >
> > > > In my opinion this is like wondering whether one should do standard
> MD
> > or
> > > > free energy calculations, or explicit vs implicit solvent, or for
> that
> > > > matter QM vs MM. Multiple MD and long continuous MD are just two
> > different
> > > > tools, and which one is the "right" tool depends completely on the
> > problem
> > > > you are trying to solve, and what sort of data it requires. The best
> > answer
> > > > is of course to do multiple very long MD, but I believe that the key
> to
> > > > success in this area (or any other where the tools are not fully
> > mature) is
> > > > to recognize that compromises must often be made, and to carefully
> > choose
> > > > the ones that have the least impact on your specific goals for the
> > project.
> > > > For a reviewer to say that in all cases multiple short MD is better
> > than
> > > > long MD makes no sense to me. That being said, I am very skeptical of
> > > > studies where there is no attempt to quantify precision.
> > > > carlos
> > > >
> > > >
> > > > On Wed, Mar 5, 2014 at 9:33 AM, Soumendranath Bhakat <
> > > > bhakatsoumendranath.gmail.com> wrote:
> > > >
> > > > > Dear Amberists;
> > > > >
> > > > > We have reported long range continuous MD simulations (50ns) in
> many
> > of
> > > > our
> > > > > research communications. But we observe that some journals and
> > reviewers
> > > > > are very much critical of continuous MD simulations and asked for
> > > > multiple
> > > > > MD simulations.
> > > > >
> > > > > But recently in a debate many people put different views on
> multiple
> > MD
> > > > > simulations and as per their view this multiple MD simulation does
> > not
> > > > > provide a great insight than continuous MD (50/100ns sampling).
> Some
> > > > people
> > > > > say in positive aspect to multiple MD saying that it covers a large
> > > > > conformational space.
> > > > >
> > > > > Majority of people agreed that if you are doing long range
> > continuous MD
> > > > > and proper post dynamics analysis thats enough to demonstrate
> maximum
> > > > > points related to motions of a biological system.
> > > > >
> > > > > As a continuous learner my question is to AMBER community that
> which
> > one
> > > > is
> > > > > preferred a long range continuous MD or corresponding Multiple MD
> > > > > simulation?
> > > > >
> > > > > As there are numerous numbers of paper on continuous MD rather
> than a
> > > > very
> > > > > few multiple MD papers on aspects like conformational analysis and
> > etc.
> > > > so
> > > > > which one is the best to go with.
> > > > >
> > > > > Please put justification in support of your argument. We experience
> > that
> > > > > some journal and reviewers always point out to do multiple MD over
> > > > > continuous MD simulation,but in maximum cases people accept long
> > range
> > > > > continuous MD.
> > > > >
> > > > > Thanks & Regards;
> > > > > Soumendranath Bhakat
> > > > > Co-Founder Open Source Drug Design and In Silico Molecules (
> > > > > www.insilicomolecule.org)
> > > > > UKZN, Durban
> > > > > Past: Birla Institute of Technology,Mesra, India
> > > > > --
> > > > > Thanks & Regards;
> > > > > Soumendranath Bhakat
> > > > > _______________________________________________
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> > > > > AMBER.ambermd.org
> > > > > http://lists.ambermd.org/mailman/listinfo/amber
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> > > >
> > >
> > >
> > >
> > > --
> > > ================================ Current Address
> =======================
> > > Brian Radak : BioMaPS
> > > Institute for Quantitative Biology
> > > PhD candidate - York Research Group : Rutgers, The State
> > > University of New Jersey
> > > University of Minnesota - Twin Cities : Center for
> > Integrative
> > > Proteomics Room 308
> > > Graduate Program in Chemical Physics : 174 Frelinghuysen Road,
> > > Department of Chemistry : Piscataway, NJ
> > > 08854-8066
> > > radak004.umn.edu :
> > > radakb.biomaps.rutgers.edu
> > > ====================================================================
> > > Sorry for the multiple e-mail addresses, just use the institute
> > appropriate
> > > address.
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>
>
>
> --
> Thanks & Regards;
> Soumendranath Bhakat
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--
Thanks & Regards;
Soumendranath Bhakat
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Received on Mon Mar 17 2014 - 04:30:04 PDT
