AMBER Archive (2004)

Subject: Re: AMBER: FEP along a reaction coordinate in sander

From: David A. Case (case_at_scripps.edu)
Date: Wed Dec 01 2004 - 11:38:45 CST

On Wed, Dec 01, 2004, Tomasz Borowski wrote:
>
> I'd like to do FEP calculations along (ab-initio)
> reaction path for a small organic system in water.
> (to get the solvation contribution to the activation
> free energy). Let's say I have the coordinates for
> several points along this path with corresponding
> RESP charges. Can I use sander to do TI along this
> path? I assume I can perturb the charges and VDW
> parms, but can I change the geometry when changing
> lambda?
>

If you haven't already done so, you should map out an approximate solvation
profile by putting each of your coordinate sets into a continuum solvent,
using GB or PB methods. This will give you a very quick intial idea of
sorts of solvation free energies you should be expecting to find.

To use an explicit solvent model, you would do the analogous calculation,
expect that for each coordinate set you would carry out free energy
simulations that convert each snapshot to "nothing" (in both gas-phase and in
solution). This will provide values that may or may not be more accurate, and
is orders of magnitude more difficult (both in terms of computer time, and in
terms of the manual setup and analysis of all of these calculations.) This
is why I made the recommendation in the first paragraph: be sure that you
really think you are going to learn something before embarking on this task.

There is no ready way that I can see to change the geometry during each of the
free energy calculations.

After you are done, you could write up a nice tutorial on how everything went,
so that others can benefit :-)

...good luck...dac

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