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Science 9 January 2004:
Vol. 303. no. 5655, pp. 186 - 195
DOI: 10.1126/science.1088172
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Review

How Enzymes Work: Analysis by Modern Rate Theory and Computer Simulations

Mireia Garcia-Viloca,1 Jiali Gao,1 Martin Karplus,2* Donald G. Truhlar1*

Advances in transition state theory and computer simulations are providing new insights into the sources of enzyme catalysis. Both lowering of the activation free energy and changes in the generalized transmission coefficient (recrossing of the transition state, tunneling, and nonequilibrium contributions) can play a role. A framework for understanding these effects is presented, and the contributions of the different factors, as illustrated by specific enzymes, are identified and quantified by computer simulations. The resulting understanding of enzyme catalysis is used to comment on alternative proposals of how enzymes work.

1 Department of Chemistry and Supercomputing Institute, University of Minnesota, Minneapolis, MN 55455, USA.
2 Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA02138, USA, and Laboratoire de Chimie Biophysique ISIS, Université Louis Pasteur, 67000 Strasbourg, France.

* To whom correspondence should be addressed. E-mail: marci{at}tammy.harvard.edu, truhlar{at}umn.edu

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