[gmx-users] Is the PMF from "gmx wham" a free energy curve?

[Alexander Björling]

Dear users,

I have a question about how to interpret (rather than about how to perform)
a GROMACS calculation.

I have calculated the Potential of Mean Force for separating two protein
chains, in order to estimate the free energy of monomerization for this
dimer, loosely following Justin Lemkul's tutorial. I have arrived at a PMF
which seems reasonable and robust according to the error estimates of "gmx
wham". The reaction coordinate is the distance in the Z-direction only,
nothing is position restrained, and there is good overlap between the 2 ns
windows.

My question: is the resulting PMF a correct estimate of the free energy of
monomerization, or are there missing entropic terms due to the
translational confinement?

Google turns up a JACS paper (dx.doi.org/10.1021/ja2060066), claiming that
the missing entropy is as large as 15-30 kcal/mol, which seems very high to
me:

"The PMF is expected to decrease after the monomers are completely
dissociated because of the gain in translational and rotational entropy.
According to previous reports, this entropy gain is anticipated to be on
the order of 50-100 cal/(mol K). Thus at 300 K the PMF is expected to
decrease 15-30 kcal/mol upon dissociation."

Is this true?

Thanks,
Alex