[gmx-users] T-coupling: System vs. Protein Sol?

[David Mathog]

David Mobley <dmobley at gmail.com> wrote:

> 
> Flexibility is always desirable. For example, in free energy calculations,
> sometimes one group (i.e. part of the protein, or a small molecule) is
> decoupled or partly decoupled from the rest of the system.

If the model is a box full of protein and solvent how does a part
of that protein, or a small molecule, get out of thermal
equilibrium with the rest of the system? 

Oh, I think I see. It has nothing to do with real proteins in 
real solvent and everything to do with the limitations of
the simulation.  The effect is discussed at the very end of
3.4.5 on page 24.  Where it says:

In GROMACS temperature coupling can be performed on
groups of atoms, typically a protein and solvent.
The reason such algorithmes were introduced is that energy
exchange between different components is not perfect,
due to different effects including cutoffs etc. If
now the whole system is coupled to one heat bath,
water (which experiences the largest cutoff noise)
will tend to heat up and the protein will cool down.
Typically 100 K differences can be obtained. With the
use of proper electrostatic methods (PME) these difference
are much smaller but still not negligable. The
parameters for temperature coupling in groups
are given in the mdp file. One special case should
be mentioned: it is possible to T-couple only part
of the system (or nothing at all obviously). This
is done by specifying zero for the time constant 
(tau sub T) for the group of interest.

So knowing that Gromacs has this nonphysical effect during
simulation (proteins don't freeze while simultaneously
boiling the solvent around them) the separate coupling factors
were introduced so that those two types of molecules could be
locked separately to a given bath temperature.

What the manual doesn't say, or say very clearly anyway, is
what happens to two or more protein chains, or DNA and protein,
in the same temperature group.  Is it necessary to break
each chain off into its own coupled group?  Does DNA in the
same coupling group as Protein drive the temperatures of
each molecule in different directions?

Thanks,

David Mathog
mathog at caltech.edu
Manager, Sequence Analysis Facility, Biology Division, Caltech