FEP of water molecule in binding pocket

From: Monika Sharma (monsharmail_at_gmail.com)
Date: Wed May 28 2014 - 15:35:33 CDT

Hello NAMD-Users,

I am doing FEP calculation for disappearance of a water molecule bound in
the binding pocket of an enzyme. I am facing problem that as the water
interaction reduces in the binding pocket, another water molecule from
nearby site is entering the binding pocket, and messing up with the free
energy values.

I was thinking to somehow restrain other molecules from entering the
pocket. But I have some doubts before I proceed:

1. Though I came up with idea of restraining the entrance of any thing
within the binding pocket, is restraining the only option for the problem

2. How can I implement this kind of restraints in NAMD? Should I take leads
from the bubble formation tutorial provided for implementation of
user-defined forces? or is there a way I can use colvar to do this?

3. In the above case, if I put reflective surface of the bubble (either by
tclforces or colvars), there will be addition of repulsive terms to FEP,
which I think will be hard to calculate? Am I correct or is there a way to
account for it so that I can later subtract it from FEP?

I will really appreciate if anyone could guide me through. Thanking in


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