Hi,
I am trying to use AMBER pmemd TI using soft-core potential, to do one-step
mutation transformation from a charged residue to a neutral one on a
protein. The problem would be that because I have both of the residues at
the beginning of the simulation (pmemd), I will use counterions to
neutralize the system, but actually, with this transformation, I will
change the system from a neutral state to a charged state. What kind of
thermodynamic cycle should I use to capture just the free energy of the
mutation of the residues??? And how should I deal with this problem of
going to a charged state??
I've read multiple opposing ideas, but the best ones would be mutating the
counterion to water at the same time, and then doing the same
counterion-water transformation in the same box without solute, then
subtract the first delta G from the second. I should use restraints on
those water and counterion to keep them in the bulk, and if agree, should I
use the same restraints in the box without solute? Does it make sense to
use restraints on those while using NPT simulation for production?
Another method would be disappearing the counterion in the same procedure.
What are your thoughts on that?? Would you prefer to do it in three step
transformation?? if yes, how?
Best
[image: Mailtrack]
<
https://mailtrack.io?utm_source=gmail&utm_medium=signature&utm_campaign=signaturevirality5&>
Sender
notified by
Mailtrack
<
https://mailtrack.io?utm_source=gmail&utm_medium=signature&utm_campaign=signaturevirality5&>
03/15/19,
2:27:53 PM
_______________________________________________
AMBER mailing list
AMBER.ambermd.org
http://lists.ambermd.org/mailman/listinfo/amber
Received on Fri Mar 15 2019 - 07:00:03 PDT
