[gmx-users] solvation free energy

[Daniele Veclani]

Then as I had already calculated the free energy in a box with solute and
solvent with the option couple-intramol = no,  I already have the
solvatation free energy correct, Is it right??

D.V.

2015-07-17 18:10 GMT+02:00 Justin Lemkul <jalemkul at vt.edu>:

>
>
> On 7/17/15 12:08 PM, Justin Lemkul wrote:
>
>>
>>
>> On 7/17/15 12:06 PM, David van der Spoel wrote:
>>
>>> 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?
>>>
>>>
>> We have not done a comparison.  In CHARMM, we always explicitly do gas
>> phase,
>> but that is by necessity.  We don't have an analogous
>> "couple-intramol"-style
>> behavior.  It could probably be done, but we have an established protocol
>> that
>> has been used for years that is rock solid.
>>
>>
> I would also agree that there would be massive errors for a polarizable
> force field in this case due to environmental response.  I assume, for now,
> most people are using additive models.  In fact, until I have actually
> tested the free energy code with our Drude model, it is explicitly disabled
> by grompp.
>
>
> -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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