Re: [AMBER] neutralizing systems for AMBER TI

From: Jason Swails <>
Date: Thu, 25 Sep 2014 10:20:41 -0400

On Sep 24, 2014, at 7:02 PM, Lawrenz, Morgan <> wrote:

> Hi all,
> For setting up a residue mutation relative free energy calc in AMBER14 with TI/FEP, I need to neutralize my system.
> The setup in leap requires a combined file with the 2 full proteins, and I wasn't sure whether I use the real net charge on a single protein for adding counter ions or to use the combined charge? I'd think just ions for a single protein, despite leap complaining that the combo structure and topology file isn't neutralized, but wanted to confirm.

Assuming of course you are running an explicit solvent calculation with plans to use PME, I would say pick one state to “neutralize” and do that (I typically add enough ions to neutralize and then some more to model a solution with some salt).

Having one state carry a net charge of +/-1 is not really a problem for PME simulations due to the fact that most (all?) implementations use what amounts to a uniform, net neutralizing plasma smeared across the entire unit cell. Since most thermodynamic cycles require you to do some sort of reference calculation, as long as you do the same charge transformation in both legs of the cycle, you should be fine.

There has been some discussion regarding net charge artifacts on this list recently (along with some citations), so if you’re concerned you can try to find that discussion. The summary as I recall is that the artifacts are most pronounced for small unit cells.


Jason M. Swails
Rutgers University
Postdoctoral Researcher
AMBER mailing list
Received on Thu Sep 25 2014 - 07:30:02 PDT
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