[gmx-users] Re: FEP

[Chris Oostenbrink]

Hello,

In principle, I think one can do this with FEP and TI, but there will be 
several things to take into account.  What you are basically doing is 
calculating the free energy of 'solvating' the ions in water and in a 
protein environment. In water, the solvation of a singly charged sodium 
ion will give you roughly 480 kJ/mol. In the protein, I would expect you 
get something of the same order, and then you subtract these two big 
numbers and it will be difficult to get an accurate estimate of the 
difference.

There will indeed be many electrostatic effects. I have seen a nice 
manuscript by Kastenholz and Huenenberger which is in press with J. 
Chem. Phys. (you'll find it on www.igc.ethz.ch -> publications). They 
have established exactly which corrections one would have to apply to 
calculate the solvation free energy of an ion using different methods 
(Straight cutoff, reaction field or lattice sum methods). Some of these 
correction terms may cancel if you look at a free energy difference, 
others may not...

As a general comment: don't use slow growth, as that is a 
non-equilibrium method and can by definition not give correct results 
(if you do a single run). Depending on how you would do the 
PMF-calculation, you will run into the same problem. If you use soft 
atoms, then you do not really have to split up the Van der Waals and the 
electrostatics.

Good luck,

Chris