Date: Fri, 12 Jul 2002 09:00:11 -0700
From: "David A. Case"
Subject: Re: counter-ions in FEP

On Thu, Jul 11, 2002, Christophe L M J Verlinde wrote:

> I would like an opinion on the following FEP simulation:
> My protein has a net charge of +3. In my simulations
> with explicit TIP3P water I usually add counterions to
> obtain a neutral system. However, now I am faced with
> performing a FEP simulation in which a neutral ligand
> is changed into an isosteric ligand with net charge -1.
> Should I keep the system neutral in both states of the FEP?
>

This is neither possible nor desirable in calculating "charging free
energies" (where the system charge is changing.) See, e.g.
Darden, Pearlman and Pedersen, J Chem Phys 109: 10921 (1998). In
general, it is best to use a method like Ewald or PME for these
sorts of calculations, since the long-range electrostatic contributions
can be significant.

..hope this helps...dac