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Summary: Charges on protein

Arthur Wang arthur at ipc.pku.edu.cn
Sun Jan 28 09:21:31 EST 1996

Dear Netters,

About a week ago, I posted the question "Charges on protein". Now I have 
received three answers and they are proved to be very valuable. I am 
trying to compare them at present. Please feel free to express your opinion.

My original question is:

It is well known that the electrostatic interactions is one of the most
important features in ligand-receptor binding. To calculate it, partial
charges of both the ligand and the receptor (usually a protein molecule)
are needed to be integrated into the Coulomb formula. If the ligand is a
small, common organic molecule, relatively reliable values could be
obtained by using semi-empirical algorithm. But the charges on the protein
remain as a stumbling block. At present, many people use residue charge
templates, which are derived from the quantum mechanical results of three
peptides.  The drawback of doing so is obvious.

So my question is, is there any better way to get the partial charges on
the protein? Any experience? Any ideas? Pointers to any literature are
also appreciated.

Here are the answers:
From: lou at scripps.edu  (Lou Noodleman)

Dear Arthur,
We use PARSE charges due to Sitkoff,Sharp,Honig, J.Phys.Chem.1994,98,
pages1978-1988, with good success.
Lou Noodleman
Molecular Biology
The Scripps Research Institute
La Jolla, CA 92037

From: luciano at giotto (Luciano Brocchieri)

Dear Arthur:
I am not sure this is not what you don't want to use, but I feel
comfortable with the AMBER forcefield. I can suggest to refer to
Cornell et al. (1995) A second generation force field for the simulation
of proteins, nucleic acids, and organic molecules. J.Am.Chem.Soc.,
117,5179-5197, and reference therein. Best wishes,

Luciano Brocchieri
(luciano at gnomic.stanford.edu)

From: dopearso at magnus.acs.ohio-state.edu (Douglas C Pearson)

the way that i've seen used most often (and have started using myself, in
protein-protein docking problems) is one algorithm or another of assigning
charges to residues through pKa calculations.  usually this will involve (in
its simplest form) placing formal charges on only the titrable atoms in the
protein (oxygen atoms on carboxyls, nitrogen atoms on arginines, lysines and
histidines, etc.), calculating a potential field over the whole atom,
converting this potential field to pKa difference, and iterating the thing
until you get constant pKa's over all residues after an iteration.  you use the
pKa to find the charge on each atom.

my current favorite software of the moment, scott northrup's macrodox, uses the
algorithm of matthew and gurd (methods in enzymology, 130:413).  there are also
articles from yang et. al. (proteins 15:252) and gilson (proteins 15:266...yes,
these articles are in the same issue, back to back!) describing different
viewpoints on the same subject.

hope this helps.  be sure to e-mail me if you need any further info...

reply-to:  dcp at hobbes.biosci.ohio-state.edu
chuck pearson - dopearso at magnus.acs.ohio-state.edu
osu biophysics program, daddy of amelia catherine pearson.



_/   Arthur Wang                     Doctoral Candidate   _/
_/   Molecular Design Lab                                 _/
_/   Institute of Physical Chemistry, Peking University   _/
_/   Beijing 100871, P.R.China                            _/
_/                                                        _/ 
_/   E-mail: arthur at ipc.pku.edu.cn                        _/
_/   Tel: 86-10-2751490    Fax: 86-10-2751725             _/
_/   WWW: http://www.ipc.pku.edu.cn/arthur/home.htm       _/

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