[gmx-developers] Coming on to help in GROMACS development

[Michael Shirts]

Sorry for the delayed response!

> What do you mean with decoupling?

What I meant was that if you use a free energy perterbation to a
molecule in a larger system, at least in GROMACS 3.1.4, the
intramolecular terms would also be lambda dependent.  If you were
interested in the solvation free energy of octanol, for example, this
wouldn't be good, since one end of the molecule wouldn't be able to
"feel" the other end when lambda became zero.  You could do another
simulation turning off all the terms in the vapor state, but that's
becomes difficult and annoying.

It's actually possible to work around this for the Lennard-Jones
potential, by defining individual ij terms, but not for the Columb
part.  By making slightly different neighborlists, however, it's
fairly easy to do, and is what I implemented.

> I have recently implemented free-energy support for Ewald and PME.
> Also I have added reaction-field corrections for the exclusions,
> with makes free-energy completey correct with RF.

I assume these code changes are you in the CVS version, correct?

> What kind of restraints?
> Position restraints now also support free-energy?
 
Yes, position restraints.   For example, in the ligand binding paper
we submitted, we use a harmonic restraint in the unbound state to make
the sampling of that state simpler, and turn this restraint off as a
function of labmda.  We can then correct for the restrained state
analytically.

Cheers,
Michael