[gmx-users] Single long simulation versus multiple short

Thomas Evangelidis tevang3 at gmail.com
Wed Jul 27 10:27:38 CEST 2011

Hi Tom,

1 ns sounds far too small to explore the various conformational states of a
protein of that size, and even worse if you expect the ligand to find it
lowest-energy conformation/position (unless you have placed it where it
binds). Perhaps you should consider enhanced sampling techniques like
metadynamics, accelerated MD, the adaptive biasing force method,
conformational flooding, hyperdynamics, etc. There is a plugin for GROMACS
(works for other MD engines as well) to perform metadynamics variations
named "PLUMED". At their website (www.plumed-code.org) you can find many
papers about metadynamics, but here are a few ones to start from:

G. Bussi, F. L. Gervasio, A. Laio, M. Parrinello, "Free-energy landscape for
beta hairpin folding from combined parallel tempering and metadynamics", J.
Am. Chem. Soc. 128 (41) (2006) 13435–41.

] C. Camilloni, D. Provasi, G. Tiana, R. A. Broglia, "Exploring the protein
G helix free-energy surface by solute tempering metadynamics", Proteins 71
(2008) 1647.

S. Piana, A. Laio, "A bias-exchange approach to protein folding", J. Phys.
Chem. B 111 (17) (2007) 4553–9.

To get a flavor about the time scales that a ligand needs to find its
lowest-energy conformation/pocket with unguided MD simulations, have a look
at this recent letter:

J Am Chem Soc. 2011 Jun 22;133(24):9181-3. Epub 2011 May 13. "How does a
drug molecule find its target binding site?", Shan Y, Kim ET, Eastwood MP,
Dror RO, Seeliger MA, Shaw DE.

hope this helps,

On 27 July 2011 02:23, Tom Dupree <t.dupree at unsw.edu.au> wrote:

> Greetings all,
> I am quite interested in this discussion, and wondered if some people would
> like to add how they would assess the length their MD simulations. I am
> currently simulating HIV-1 RT for 1 ns and seem to have very flat energy
> profiles for almost anything (energy wise) I care to measure and yet ligand
> position/conformation continues to change throughout the simulation.
> Tom
> Widya Desmarani wrote:
> > Dear gromacs user,
> >
> > I have been trying to look for an answer for my following question from
> > our forum but still couldn't manage to find one. Probably it is trivial
> > but I am not sure.
> >
> > Instead of running a single relatively long simulation (say for about 30
> > ns), is it acceptable if we simulate multiple short simulations (say 15
> > simulations where each of them is 2 ns), and then, all the resulted
> > trajectories are merged/concatenated into one single trajectory with the
> > amount of total simulation 30 ns? I am interested in investigating bulk
> > properties of liquid, such as compressibility, diffusion, and dielectric.
> >
> There is no need to concatenate the trajectories, and moreover it may give
> you a
> misleading result.  Every simulation needs time to equilibrate.  In the
> limit of
> infinite sampling, all simulations should converge to the same properties,
> on
> average.  Whether or not your simulation can produce stable properties in 2
> ns
> is something you'll have to decide.  If 2 ns is insufficient, then you're
> still
> not collecting data that are as reliable as you would get from a longer
> simulation.
> Multiple simulations from independent starting velocities and/or
> configurations
> are generally expected.  A single simulation does not necessarily tell you
> the
> whole truth.
> -Justin
> --
> ========================================
> Justin A. Lemkul
> Ph.D. Candidate
> ICTAS Doctoral Scholar
> Department of Biochemistry
> Virginia Tech
> Blacksburg, VA
> jalemkul[at]vt.edu | (540) 231-9080
> http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin
> ========================================
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Thomas Evangelidis

PhD student

Biomedical Research Foundation, Academy of Athens

4 Soranou Ephessiou , 115 27 Athens, Greece

email: tevang at bioacademy.gr

          tevang3 at gmail.com

website: https://sites.google.com/site/thomasevangelidishomepage/
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