Re: [AMBER] Wham tolerance

From: Jason Swails <>
Date: Mon, 18 Nov 2013 17:41:21 -0500

On Mon, Nov 18, 2013 at 5:17 PM, Fabrício Bracht <>wrote:

> Yes. They are overlapping. The force constant is the lowest that allowed me
> to properly sample high energy regions. The differences in the free energy
> values I get with the different tol values are proportional to the amounts
> of zeros that I use for tol. For example:
> Tol Value at 0.584444 Angstrom
> 0.01 6.559799
> 0.001 7.006187

These are very large tolerance values. I would never use values this large.

> 0.0001 7.051056
> 0.00001 7.055565
> 0.000001 7.056019
> 0.0000001 7.056064
> 0.00000001 7.056069
> 0.000000001 7.056069

This seems much more reasonable. I think my default tolerance is 10^-5 or
10^-6, or something to that extent. In any case, your free energies change
less than 10^-3 kal/mol from tolerance = 10^-4 to 10^-9, which suggests
that any value in that range is reasonable.

I believe Alan Grossfield's program will also do bootstrapping to estimate
uncertainties. This is worth doing in my opinion, although if you _really_
want reliable uncertainty estimates you'll want to use a better estimator
than WHAM. MBAR (the multistate Bennett acceptance ratio) has been shown
to be a superior estimator to the free energy than WHAM (and equivalent in
the limit of infinite sampling), and an advantage of MBAR is that you get
the uncertainties directly.

Is this normal?

It doesn't look unusual to me.

Good luck,

Jason M. Swails
Rutgers University
Postdoctoral Researcher
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Received on Mon Nov 18 2013 - 15:00:03 PST
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