[gmx-users] solvation free energy

[David van der Spoel]

On 17/07/15 17:55, Justin Lemkul wrote:
>
>
> 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.
>
If I understand that correctly then the protocol ignores the difference 
in intramolecular energy between gas-phase and solvation. This is 
probably OK for small and rigid molecules but not necessarily for larger 
or flexible molecules. When using polarizable force fields it will 
probably induce a significant error. Have you tried this yet?

> -Justin
>


-- 
David van der Spoel, Ph.D., Professor of Biology
Dept. of Cell & Molec. Biol., Uppsala University.
Box 596, 75124 Uppsala, Sweden. Phone:	+46184714205.
spoel at xray.bmc.uu.se    http://folding.bmc.uu.se