Re: [AMBER] which methods calculate the binding energy most accurate

From: Aron Broom <>
Date: Thu, 12 Apr 2012 00:49:09 -0400

A lot of people may suggest the MM-PBSA method, which I believe is rather
fast compared to other options, but the accuracy may be questionable,
particularly if you aren't actually confident about what the bound 3D
structure is for your systems.

Overall this is a really tough problem, and certainly not something with a
standard answer. If you want the greatest accuracy, I would suggest
considering something like replica-exchange metadynamics (also known as
well-tempered metadynamics if you are doing a literature search). It will
largely alleviate (hopefully) the problem of not knowing the exact bound
3D-structure (or perhaps there is no single bound structure if your peptide
is highly flexible in which case this will work well also), it will give a
highly accurate answer (within the limitations of the force-field of
course), but it will take quite a long amount of simulation time to
converge (relative to many other methods, and will require at least two
simulations running synchronously). I don't think AMBER11 has this
facility natively built in, but you can use the PLUMED plugin ( with AMBER11 and setup this
kind of calculation.

Maybe someone else has some useful comments on what I've said.


On Wed, Apr 11, 2012 at 9:21 PM, Acoot Brett <> wrote:

> Dear All,
> There is a series of protein-peptide dimer, in the dimers all the protein
> are the same protein, with about 400 aas. In the dimer, the peptide can be
> any one of a series of highly consered peptides with about 15 aas.
> There is difficulty to get accurately the binding energy between the
> protein and the peptide. Or the binding energy could be got, but caused by
> the assay method the measured binding energy differnece among different
> dimers cannot be explained by the correspdonding dimer 3-D structural
> difference.
> I plan to use AMBER to calculate the binding energy between the peptide
> and the protein in each dimer.
> Will you please give me some comment on the available AMBER calculation
> methods, corresponding calculation accuracy and the corresponding
> calculation time length for the calculation of the binding energy?
> Cheers,
> Acoot
> _______________________________________________
> AMBER mailing list

Aron Broom M.Sc
PhD Student
Department of Chemistry
University of Waterloo
AMBER mailing list
Received on Wed Apr 11 2012 - 22:00:03 PDT
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