Re: [AMBER] Normal mode analysis for entropy calculation in MM/GBSA

From: David A Case via AMBER <>
Date: Sat, 24 Sep 2022 09:23:16 -0400

On Fri, Sep 16, 2022, He, Amy via AMBER wrote:
>1 Could you direct me to a documentation or literature that talks about the
>formulation of the normal mode analysis in Amber? Specifically, what is the
>force constant matrix or the harmonic potential that’s being used in the
>normal mode analysis?

Here are a couple of papers:

%A D.A. Case
%T Normal mode analysis of protein dynamics
%J Curr. Opin. Struct. Biol.
%V 4
%P 285-290
%D 1994

%A R.A. Brown
%A D.A. Case
%T Second derivatives in generalized Born theory
%J J. Comput. Chem.
%V 27
%P 1662-1675
%D 2006

(The second paper is quite technical, just giving details of how GB theory
is implemented.)

Basically, the force constant matrix is constructed from the second
derivative of the Amber potential energy function.

>2 My system is a bit too large and it probably won’t be affordable to
>compute the normal mode entropy for the entire system… I have read about
>using normal mode analysis on a truncated protein-ligand system to
>calculate the relative binding entropy. I was wondering, if we need to
>break the protein into pieces, how would that impact the calculation of the

I don't have any experience with this. Here is an (old) approach to
truncation that describes tests on accuracy:

%A J. Kongsted
%A U. Ryde
%T An improved method to predict the entropy term with the MM/PBSA approach
%J J. Comp.-Aided Mol. Des.
%V 23
%P 63-71
%D 2009

>3 Do we need to use a trajectory (multiple snapshots), or can it be just
>one snapshot?

To get an average entropy, you would generally want to use multiple
snapshots. But the fluctuations in the results between snapshots are
generally(!?!) pretty small, so you may not need a large number of
snapshots. First try to get it to work on just one, then explore how much
the results vary from snapshot to snapshot on your system.

....good luck...dac

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Received on Sat Sep 24 2022 - 06:30:03 PDT
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