

Jeremy:

   One particularily interesting reference that relates to the problem of
predicting changes in structure and binding properties of mutant proteins is
by Wilson et al.[1]  Using molecular mechanics with a solvent correction plus
a protein side-chain rotamer library, these authors were able to design a
mutant enzyme with altered substrate specificity and good selectivity. 

   As Wilson et al. have done, you will probably need to consider alternative
sied-chain conformations of the residue that has mutated as well as the
immediately surounding residues.  This is especially true of surface residues.
For this purpose, the rotamer library of Dunbrack and Karplus is the most
up-to-date.[2] 

    This library along with a Fortran program for reading it are available
directly from the author ([email-masked]) or from anonymous ftp
(babar.ucsf.edu).  Finally, if you have access to Sybyl, I have written an SPL
for assignment of sidechain conformation, given the coordinates of the
backbone based on the Dunbrack and Karplus rotamer library.  This is available
via anonymous ftp (extreme.chem.rpi.edu), and the file is
/pub/sybyl/spl/sarl.spl.Z.  where SARL stands for Sidechain Assignment by
Rotatmer Library.  This script iteratively explores sidechain conformations
taken from the rotamer library which minimize the number of bad contacts.  The
script also allows you to restrict the conformer search to a subset of
residues. 

[1]  Wilson, C.; Mace, J. E.; Agard, D. A. Computational method for the design
     of enzymes with altered substrate specificity.  J. Mol. Biol. 1991, 220,
     495-506. 
[2]  Dunbrack, R. L., Jr.; Karplus, M. Backbone-dependent rotamer library for
     proteins.  Application to side-chain prediction.  J. Mol. Biol.  1993,
     230, 543-574. 

   I hope you find these references helpful.

   Ciao,

Konrad

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| Konrad Koehler              |  Computational Chemistry Group     |
| internet:  [email-masked]  |  Department of Medicinal Chemistry |
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