Re: [AMBER] charges for ion and surrounding residues at the active site

From: FyD <>
Date: Tue, 20 Mar 2012 12:55:07 +0100

Dear Jorge,

You need to extract the "active site" from the protein; this
'extracted' active site is a 'part' of the protein i.e. a _molecular

A molecular fragment does not exist in quantum mechanics (QM); so this
molecular fragment as to be transformed (using well chosen capping
groups) into a _whole molecule_ for the geometry optimization (i) and
MEP computation (ii) steps performed by QM. Then, during the charge
fitting step (iii) specific charge constraints (intra- and/or
inter-molecular charge constraint(s); See are used to generated the
wanted _molecular fragment_, which was originally extracted from the

Key points are:
- checking that the optimized geometry generated during the geometry
optimization (i) using the capped molecular fragment is similar to
that in the protein. Here, you can test different capping group
approaches and/or use geometrical constraint(s) during the geometry
optimization (i).
- comparing the charge values in presence and in absence of these
intra- and/or inter-molecular charge constraint(s) during the charge
fitting step so that these constraints do not impact 'too much' the
charge fitting step (iii).

R.E.D. generates the required molecular fragment(s) in the mol2 file
format (FF library) starting from P2N input file(s) (where the pieces
of information required to build the wanted fragment are provided by
the user; see
At the end, this FF library is loaded in the LEaP program with the
Amber Force Field Topology DataBase to be able to generate the
prmtop/prmcrd files for the entire protein.

all these are only generalities ;-)

regards, Francois

> I have a protein to which I wanted to make some molecular dynamics
> and co-factor binding energy calculations. Nevertheless, the active site
> has a Calcium ion. I refer to i) J Mol Biol. 2007 February 16; 366(2):
> 687-701; ii) Journal of Structural Biology Volume 157, Issue 3, March
> 2007, Pages 444-453; iii) J Chem Phys. 2010 Apr 7;132(13):131101; which,
> in general, suggest that more properly the charges for the ion and the
> surrounding residues (including the co-factor?) should be improved with
> a QM calculation beforehand. Also, I see the tutorials a)
> ; b)
> and c)
> . As far as I
> understand, I should submit to a QM program an excerpt of the protein,
> id est, the ion and the closest (complete to the N and C=O) residues
> (maybe any residue which is within 6 A from the ion - so I have a
> molecular fragment(s)) and then get from the QM program the modified
> parameters for them all (including charges). What I could not figure
> still clearly is a step by step tutorial to do this. For this kind of
> molecular fragment (ion + surrounding residues - which most are not
> connected to each other) might the tutorial
> fulfill all
> requirements? In this case it does not resort to Gaussian, should this
> be enough to parametrize the residues and ion to be incorporated into
> the force filed and do the dynamics? I would be happy to read further
> references and tutorial on how to do this.

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Received on Tue Mar 20 2012 - 05:00:03 PDT
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