14 May 2009
Prof. Walter Thiel (Max-Planck-Institut für Kohlenforschung, Mülheim an der Ruhr, Germany)
Theoretical Studies of Enzymatic Reactions
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,[1,2] the lecture will describe some of our recent work on biocatalysis by enzymes, in particular cytochrome P450cam.[3-8] Topics include the electronic structure of P450cam intermediates, two-state reactivity in the oxygenation reaction, the biocatalytic role of single water molecules, revised mechanisms for the formation of the Compound I intermediate, and the competition between coupling and uncoupling reactions in the wild-type enzyme and several mutants. P450cam will thus serve as an example of the chemical insights and the improved mechanistic understanding that can be provided by QM/MM calculations. Time permitting, the lecture will also address theoretical studies that rationalize the improved enantioselectivity of lipase mutants generated by directed evolution in our institute.
- H. M. Senn, W. Thiel, Top. Curr. Chem. 2007, 268, 173-290.
- H. M. Senn, W. Thiel, Angew. Chem. Int. Ed. 2009, 48, 1198-1229.
- J. C. Schöneboom, H. Lin, S. Cohen, S. Shaik, W. Thiel, J. Am. Chem. Soc. 2004, 126, 4017-4034.
- J. C. Schöneboom, F. Neese, W. Thiel, J. Am. Chem. Soc. 2005, 127, 5840-5853.
- J. Zheng, D. Wang, W. Thiel, S. Shaik, J. Am. Chem. Soc. 2006, 127, 13204-13215.
- A. Altun, S. Shaik, W. Thiel, J. Am. Chem. Soc. 2007, 129, 8978-8987.
- D. Wang, J. Zheng, S. Shaik, W. Thiel, J. Phys. Chem. B 2008, 112, 5126-5138
- M. Altarsha, T. Benighaus, D. Kumar, W. Thiel, J. Am. Chem. Soc. 2009, 131, 4755-4763.
- M. T. Reetz, M. Puls, J. D. Carballeira, A. Vogel, K.-E. Jaeger, T. Eggert, W. Thiel, M. Bocola, N. Otte, ChemBioChem 2007, 8, 106-112.