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

From: Jorge Iulek <>
Date: Tue, 20 Mar 2012 21:28:36 -0300

Thanks, Francois, for coming to help again.
I understand

is the *route to go* and programs Ante_R.E.D.-1.x & R.E.D. III.x should
suffice (besides the amber programs, of course). Now I should study and
apply the mentioned tutorial.


On Tuesday 20 March 2012 08:55 AM, FyD wrote:
> 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
> fragment_.
> 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
> protein.
> 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.
> See
> 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 - 17:30:02 PDT
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