[gmx-users] Re: FEP softcore problematics

[Berk Hess]

>Sorry about all of the confusion. Basically, the answer to this
>depends on what exactly you're doing. (I should really write all of
>this up in a tutorial soon). The way I think about it is that there
>are two fundamental principles you need to keep in mind, and you can
>do it any way you can cook up as long as you follow these two:
>(1) Always use soft core when modifying vdW interactions
>(2) Never leave charges on atoms for which you are turning off the vdW
>interactions

>Now that you mention it, I'm not entirely certain I understand Berk's
>scheme (it makes me confused, too). I still think the most
>straightforward one is my scheme: First neutralize any atoms which are
>disappearing; second, change the LJ parameters (either for insertion
>or deletion); third, modify all of the remaining charges to get where
>you want to end up at.

I think my scheme was indeed not entirely clear.
I was thinking of a way to make a symmetric sheme.
But for that one would have to make the charges
for atoms that are present both in the A and the B state go to
the average of the A and the B state for the end of step 1
and the beginning of step 3.

Anyhow it does not really matter how you do things as long
as the end states of the steps match and you obey the rules
(1) and (2) mentioned by David above. The efficiency will
not depend strongly on the scheme.
Except for a less efficient variant where one would make
all charges that change go to zero in the intermediate states,
as this would make your molecule less polar and could
affect its conformation and hydration significantly.

Berk.