[gmx-users] Re: Conceptual question: Why are MD production simulations usually run in the NVT ensemble?

[Andrew DeYoung]

Hi,

Thanks for your time.  Based on Justin's and Florian's responses, it seems
that the choice of whether to do production simulations in NpT or NVT
depends on what you're studying.  Does the following seem like a reasonable
summary of the discussion:

-- In biophysics, lab experiments are almost always performed at constant
pressure (i.e., atmospheric pressure), so NpT is the natural choice.
Moreover, in biophysics, people are often interested in particular system
states, like the folding of a protein.  These states depend on free
energies, which in turn depend on the Gibbs free energy G.  This
necessitates the use of the NpT ensemble because it is the only ensemble (I
guess?) that allows control over G.

-- In physical chemistry studies of liquids, I speculate that lab
experiments are still almost always performed at constant pressure.
However, in these types of studies, people are less frequently interested in
particular system states; hence calculation of free energies are typically
not necessary.  But just because calculation of free energies is not
necessary does not mean that NpT cannot be used.  Nevertheless, NVT is
preferable in that it avoids the use of a barostat, which can give rise to
artifacts and whose parameters are difficult to set for new compounds.

A fellow student put forth one more possible distinction between biophysics
and physical chemistry.  He pointed out that in biophysics, one often
studies macromolecules like proteins, which undergo significant structural
changes and hence undergo large changes in volume during the simulation;
hence NVT should not be used.  In contrast, in physical chemistry, one is
more often interested in small molecules.  Small molecules do not undergo
large structural changes, so the system volume is expected to vary very
little during the simulation; hence NVT is permissible.  Also, NVT is
_perhaps_ slightly less computationally expensive than NpT, so NVT should be
used when it is permissible (i.e., when folding does not occur and when
calculation of free energies is not needed).

Do you agree with this reasoning?  Do you think that protein folding leads
to large changes in system volume, whereas in liquids the system volume is
not expected to change much?  

Thanks so much!

Andrew DeYoung
Carnegie Mellon University