AMBER Archive (2004)

Subject: Re: AMBER: MM_PBSA reproduction of literature values and accuracy

From: Carlos Simmerling (carlos_at_ilion.bio.sunysb.edu)
Date: Tue Oct 26 2004 - 17:51:16 CDT

Karl,
I'm still not sure if you want a solvation free energy (corresponding to
moving the molecule from the gas phase into water), or an absolute
total free energy. total free energies aren't really meaningful, and the
zero
value for energy isn't defined in the force field (or at all). So, if
you want
a solvation free energy change, you need to define initial and final states
and then calcuate the free energy change between them. This means you
need deltaH and deltaS. It looks like you are using S, not deltaS. For
solvation
free energy, you need the solute deltaS, which is the solute entropy in
water
minus the entropy in the gas phase. I don't think you're calculating
both of those, and in fact doing that accurately is pretty challenging.
The nmode code can't even include "good" solvation in the entropy
calculation, just distance-dependent dielectric. The change in the entropy
of the water itself is (approximately) included in the GB/SA terms.

Let me know if this isn't what you are talking about.
Carlos

===================================================================
Carlos L. Simmerling, Ph.D.
Associate Professor Phone: (631) 632-1336
Center for Structural Biology Fax: (631) 632-1555
Stony Brook University Web: http://comp.chem.sunysb.edu/carlos
Stony Brook, NY 11794-5115 E-mail: carlos.simmerling_at_stonybrook.edu
===================================================================

Karl N. Kirschner wrote:

>Hi Carlos and Thomas,
> Thanks for you replies so far. From my understanding, the mmpbsa
>script is capable of calculating an absolute free energy (ie. RECPT is
>set to 1 in mmpbsa.in while Complex and Ligand are set to 0) using the
>GB model in sander. The gas-phase values are not subtracted out (GBTOT
>= GBSUR + GB + GAS, where GBSUR is the hydrophobic contribution to
>solvation free energy, GB is reaction field energy, and GAS is ELEC +
>VDW + INT). The entropy contributions are not included in GBTOT.
>
> The entropy contributions are calculated using NMODE. This is done
>for each snapshot of ethanol pulled from the explicit solvation dynamics
>(ie. on ~1000 structures). To be clear, I generate an ensemble of
>ethanol conformations using explicit solvation dynamics and then
>calculate the GBTOT and the entropy on just the ethanol (ie. the TIP3P
>waters are not included in the post trajectory mmpbsa calculation) from
>each saved structure in the ethanol_water_md.crd coordinate file.
>
> So, maybe I am trying to use mmpbsa to answer a question that I
>shouldn't. But, I was under the impression that one can calculate a
>free energy of solvation for a molecule using the mmpbsa script.
>
> Thanks again for talking this through...
>
>Cheers,
>Karl
>
>
>
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