Re: [AMBER] charged residue mutation free energy

From: Hosein Geraili Daronkola <>
Date: Fri, 12 Apr 2019 09:04:12 +0200

I tried to mutate the charged residue and the counter ion at the same time
using softcore. But the combination of the counter ion solvation free
energy and the charged residue alone is not equal to the both together.
Does anybody have any idea on how to do this??

On Fri 15. Mar 2019 at 14:32 Hosein Geraili Daronkola <>

> 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]
> <> Sender
> notified by
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> <> 03/15/19,
> 2:27:53 PM
Hosein Geraili Daronkola
Ph.D. student,
Wissenschaftspark Potsdam-Golm
Max Planck Institute of Colloids and Interfaces
Theory and Bio-Systems Department
Office K-1.119
Am M├╝hlenberg 1 OT Golm
14476 Potsdam
Phone: +49-(0)331 567-9611
Fax: +49-(0)331 567-9602
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Received on Fri Apr 12 2019 - 00:30:02 PDT
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