AMBER Archive (2007)

Subject: Re: AMBER: implicit solvent free energy calcs

From: David A. Case (case_at_scripps.edu)
Date: Thu Feb 15 2007 - 14:19:53 CST


On Thu, Feb 15, 2007, David Mobley wrote:

>
> I'm considering doing free energy calculations in implicit solvent,
> and was curious whether anyone has done anything along these lines in
> AMBER. Are you aware of any work along these lines?

Changing charges with a GB model certainly works and seems to give pretty
useful answers. See for example, a comparison between pKa calculations in
implicit and explicit solvent (both using thermodynamic integration):

%A T. Simonson
%A J. Carlsson
%A D.A. Case
%T Proton binding to proteins: pKa calculations with explicit and implicit
solvent models
%J J. Am. Chem. Soc.
%V 126
%P 4167-4180
%D 2004

We didn't try to change the non-polar part of the GB/SA model; these
calculations were for charge changes only. (This should be a good model
for pKa calculations, but would probably not be sufficient for larger
changes.)

Note also that the whole community is still struggling to get reliable
implicit solvent models. So you should be prepared to see some disappointing
results. But maybe it is exactly these sorts of calculations that would point
the way to getting better GB models....

>
> Is there any reason to think that the current free energy code would
> *not* work properly for this? Particularly, I'm thinking of changing
> or removing charges on a small molecule in the context of, say,
> hydration free energies. When it comes to the nonpolar component, I'm
> assuming that I'd actually have to modify the GB parameters for
> specific atom types in order to turn off the nonpolar interactions
> with the environment, or is there an easier way to do this?
>

Amber 9 makes changing any or all of the GB parameters easy to implement; this
would not be possible in Amber 8 or earlier. Please let us know if you see
any problems (I know you are already working with Thomas on explicit solvent
stuff).

...regards...dac
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