AMBER Archive (2006)

Subject: Re: AMBER: error estimate for free energy perturbation calculation

From: David A. Case (case_at_scripps.edu)
Date: Wed Oct 25 2006 - 13:40:47 CDT

On Wed, Oct 25, 2006, Chris Moth wrote:
> >
> >Can someone please recommend references for the estimate of error
> >(including sampling error) for the free energy perturbation calculation?
> >I want to know how reliable my delt_delt_G is, and how many trajectories
> >are necessary, how small each step should be, etc.

Note that Amber doesn't support free energy perturbation calculations (any
more), so this might not be a great place to ask. Thermodynamic integration
calculations have the advantage that one is always at equilibrium, so many of
the usual convergence criteria can be used. A careful analysis of sampling
errors is given here:

%A M.R. Shirts
%A J.W. Pitera
%A W.C. Swope
%A V.S. Pande
%T Extremely precise free energy calculations of amino acid side chain
%analogs: Comparison of common molecular mechanics force fields for proteins
%J J. Chem. Phys.
%V 119
%P 5740-5761
%D 2003

These authors do *lots* of sampling to get sampling errors in the range of
0.01 kcal/mol or so. This is overkill for most calculations, but the ideas
are the same even for much shorter calculations. [Of course, there is no
simple way to estimate the real error that arises from the fact that force
fields are not accurate enough and nuclear quantum effects are being ignored.]

I recognize that this doesn't really answer the original question (about FEP),
but it might provide a useful pointer for those doing Amber TI calculations --
maybe that will even include you in the future! :-)

...regards...dac

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