Re: [AMBER] Use of semiempirical QM/MM method in Amber to obtain free energy profile of a reaction

From: Gustavo Seabra <>
Date: Tue, 22 Feb 2011 14:53:31 -0300

Hi Dmitry

Although it is true that a real /ab-initio/ calculation would, in
principle, be preferable, /ab-initio/ estimates suffer from a great
problem: sampling. Basically, how many single-point calculations did
you have to run to get your final results? If you used Jarzynski, with
multiple realizations of the reaction, I bet they have been a lot.
Now, imagine doing that with an /ab-initio/ method, and that by itself
should provide you with good argument.

Of course, you should back your results with comparisons, for simpler
reactions, between RM1 and /ab-initio/ results. There are a number of
articles out there that compare semi-empirical with /ab-intio/ and DFT
methods and hopefully you'll find one with reaction that are related
to the one you are dealing with.

Gustavo Seabra
Professor Adjunto
Departamento de Química Fundamental
Universidade Federal de Pernambuco
Fone: +55-81-2126-7417

On Tue, Feb 22, 2011 at 1:11 PM, Dmitry Nilov <> wrote:
> Dear Amber community!
> Recently I have calculated free energy barrier of an enzymatic
> reaction using multiple steered RM1/MM MD method in Amber 10 (with
> subsequent Jarzynski exponential averaging) and the results are in
> very good agreement with experimental rate constant. However I cannot
> be quite satisfied since "ab initio" people around do not trust in
> suitability of semiempirical methods for calculation of reaction free
> energy profile.
> Could you be so kind to give me an advice or a link on appropriate
> paper to clear up my confusion!
> --
> Dmitry Nilov,
> Faculty of Bioengineering and Bioinformatics,
> Lomonosov Moscow State University
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Received on Tue Feb 22 2011 - 10:00:07 PST
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