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Abstract No.: L6
Speaker: Walter Thiel
Session: Plenary Lecture L6
Presentation date: Fri, Sep 1, 2006
Presentation time: 12:10 – 13:00

Computational Studies on Enzymes

Walter Thiel1

1 Max-Planck-Institut fuer Kohlenforschung, Muelheim, Germany

Correspondence address: Walter Thiel, Max-Planck-Institut fuer Kohlenforschung, Kaiser-Wilhelm-Platz 1, Muelheim an der Ruhr, D-45470 Germany.

Web site: http://www.mpi-muelheim.mpg.de/thiel

Keywords: Calculations, Ab Initio; Calculations, Molecular Modeling; Calculations, Semi-empirical; Computational Methods; Computer Modeling, Simulation; Enzymes; Reaction Mechanisms.

In recent years, it has become possible to model chemical reactions in large biomolecules using combined quantum mechanical / molecular mechanical (QM/MM) methods. After a general outline of the theoretical background and the chosen strategy,1 the lecture will describe selected results from our recent work on biocatalysis by enzymes, in particular QM/GROMOS investigations (QM=AM1 up to LCCSD(T0)) on p-hydroxybenzoate hydroxylase (PHBH) 2-4 and DFT/CHARMM studies on cytochrome P450cam 5-9 and fluorinase.10 These studies address the mechanism of oxygenation by PHBH, of stereospecific biohydroxylation by P450cam, and of C-F bond formation by fluorinase. The lecture will attempt to demonstrate to non-specialists how QM/MM calculations can contribute to a better mechanistic understanding of enzymatic reactions, and in particular of the role that is played by the protein environment.

1. P. Sherwood et al, J. Mol. Struct. Theochem 632, 1 (2003).
2. H. M. Senn, S. Thiel, and W. Thiel, J. Chem. Theory Comput. 1, 494 (2005).
3. J. Kastner and W. Thiel, J. Chem. Phys. 123, 144104 (2005).
4. R. Mata, H.-J. Werner, S. Thiel, and W. Thiel, to be published.
5. J. C. Schoeneboom, H. Lin, N. Reuter, W. Thiel, S. Cohen, F. Ogliaro, and S. Shaik, J. Am. Chem. Soc. 124, 8142 (2002).
6. J. C. Schoeneboom, H. Lin, S. Cohen, S. Shaik, and W. Thiel, J. Am. Chem. Soc. 126, 4017 (2004).
7. J. C. Schoeneboom and W. Thiel, J. Phys. Chem. B 108, 7468 (2004).
8. J. C. Schoeneboom, F. Neese, and W. Thiel, J. Am. Chem. Soc. 127, 5840 (2005).
9. A. Altun, V. Guallar, R. A. Friesner, S. Shaik, and W. Thiel, J. Am. Chem. Soc. 128, 3924 (2006).
10. H. M. Senn, D. O'Hagan, and W. Thiel, J. Am. Chem. Soc. 127, 13643 (2005).