[gmx-users] solvation free energy

[Justin Lemkul]

On 7/17/15 11:29 AM, Daniele Veclani wrote:
> I'm using gromacs version 5.0.4, so should I upgrade to version 5.0.5 ?
>

If you need [ pairs_nb ], yes.  But I actually don't think you do.  See below.

> I read in the manual (section 5.3.4) that can turn off the 1-4 interactions
> without ever touching the topology, by using the couple-moltype,
> couple-lambda0, couple-lambda 1, and couple-intramol keywords.
>

I think you're reading this section backwards.  Admittedly, it's a confusing 
section, so let's simplify.

If you turn off the nonbonded interactions of some molecule in water, the total 
contribution to the free energy change is composed of the solute-solute terms 
and solute-water terms.  To get the actual solvation free energy, one needs to 
correct for the solute-solute terms being turned off, which is the purpose of 
the gas-phase simulations.  Turning off interactions in vacuo tells you how much 
of the free energy change is attributed to intramolecular terms.  The difference 
between the two transformations is then the solvation free energy.

But, several years ago, this procedure became much easier in GROMACS with the 
introduction of the "couple-intramol" keyword.  It *eliminates* the need for any 
gas-phase simulations or topology hacking.  This is what the manual is trying to 
tell you.  If you run your transformations in water with "couple-intramol = no," 
then the intramolecular interactions are always full strength, so the free 
energy difference you calculate is solely attributed to solute-water 
interactions, viz. the solvation free energy.

If you *want* to make your life more difficult, set "couple-intramol = yes" and 
conduct gas-phase calculations, as well, which is what requires topology 
hacking.  I wouldn't do this.  Not only is the manual somewhat unclear, but any 
time you have to manually modify the topology, there is a potential for error. 
The free energy code attempts to make your life easy and efficient, unless you 
have some very complex protocol to do that requires lots of work.  A solvation 
energy is not one of these cases; it is straightforward with appropriate use of 
the .mdp keywords.

-Justin

-- 
==================================================

Justin A. Lemkul, Ph.D.
Ruth L. Kirschstein NRSA Postdoctoral Fellow

Department of Pharmaceutical Sciences
School of Pharmacy
Health Sciences Facility II, Room 629
University of Maryland, Baltimore
20 Penn St.
Baltimore, MD 21201

jalemkul at outerbanks.umaryland.edu | (410) 706-7441
http://mackerell.umaryland.edu/~jalemkul

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