FEP calculations - membrane protein

From: Luba Simhaev (luba.simhaev0703_at_gmail.com)
Date: Thu Dec 31 2020 - 02:45:38 CST

Dear all,
My system consists of a membrane protein which is an ion exchanger, the
protein binds three sodium ions. I would like to calculate the binding
affinity/selectivity of each ion to the protein.
My intention is to use the alchemical FEP, as implemented in NAMD.
I have some questions that I couldn't find the answers for in the tutorial
or in any publication:
1) As I understand correctly, I have to run 2 simulations (protein and ion;
ion only). In the system of the ion in water, should I use the same box
size and shape as in the protein+ion system?
2) While running FEP the Lambda is changed from 0 to 1 (forward) or from 1
to 0 (backward), should the ion be restrained to its position in the order
to avoid its displacement when the Lambda is diminishing?

I would appreciate your help.

Many thanks,

Dr. Ischakov Simhaev Luba, Ph.D.
Computational assisted drug-design unit
*Blavatnik Center for Drug Discovery*
Cohen-Porter Family United Kingdom Building
(Britannia), 1st floor
Tel Aviv University, Ramat Aviv
Tel Aviv, Israel, 6997801
Tel:+972-3-640-9842, 9654
Web-site: https://urldefense.com/v3/__http://www.bcdd.tau.ac.il/__;!!DZ3fjg!sZS2iHQ7r-d2-xjZSFUgybW1mpUqgbg6A51UUiFVwHqF-8wKKp0J-8UstjF31ck87w$ 

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