Re: [AMBER] tleap neutralization bug?

From: Jason Swails <>
Date: Mon, 15 Sep 2014 12:23:17 -0400

On Mon, 2014-09-15 at 11:45 -0400, Marcus Arieno wrote:
> Out of curiosity, what type of simulation artifacts would one expect
> if the periodic system carries a net charge? I suspect such an issue
> might give slight density problems if running NVT simulations for a
> long time, but NPT should be more or less fine.

I'll assume you're referring to "with Particle-Mesh Ewald", because the
answer to this question depends heavily on the model you're using for
the long-range electrostatics. I'll also assume you meant a problem
with NPT rather than NVT, since density fluctuations can only occur with
the former. And indeed you're right -- the most common artifacts are
pressure-related as I recall (although NVT is susceptible to some
artifacts as well).

The standard PME implementation results in what is called a "net
neutralizing plasma" for charged systems (I believe this is a
consequence of omitting the k=0 term in the reciprocal sum which is 0
for a neutral system or infinite for a charged system). This is
formally equivalent to introducing a "background" charge that
neutralizes the entire system and smearing it evenly across all of the
atoms. For small unit cells, you see a bigger effect than for larger
ones. For example, see DOI 10.1063/1.476320 from ~15 years ago.

It also seems that for highly non-homogeneous systems (like lipid
bilayers, micelles, etc.), this correction can actually increase the
preference for the ion to embed itself inside a low-dielectric region
(i.e., inside the bilayer)! See, for example, DOI 10.1021/ct400626b.

In practice, this correction is often used for calculations in which the
total charge is not fixed (a prime example being pKa calculations, such
as the model I presented in the article DOI 10.1021/ct401042b) and it
yields satisfactory behavior.

I think the discussion in the second article I linked is particularly
instructive, and if you simulate a small system you should be more

Hope this helps,

Jason M. Swails
Rutgers University
Postdoctoral Researcher
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Received on Mon Sep 15 2014 - 09:30:02 PDT
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