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Enzyme millisecond conformational dynamics do not catalyze the chemical step.

ABSTRACT: The idea that enzymes catalyze reactions by dynamical coupling between the conformational motions and the chemical coordinates has recently attracted major experimental and theoretical interest. However, experimental studies have not directly established that the conformational motions transfer energy to the chemical coordinate, and simulating enzyme catalysis on the relevant timescales has been impractical. Here, we introduce a renormalization approach that transforms the energetics and dynamics of the enzyme to an equivalent low-dimensional system, and allows us to simulate the dynamical coupling on a ms timescale. The simulations establish, by means of several independent approaches, that the conformational dynamics is not remembered during the chemical step and does not contribute significantly to catalysis. Nevertheless, the precise nature of this coupling is a question of great importance.

SUBMITTER: Pisliakov AV

PROVIDER: S-EPMC2762662 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

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Enzyme millisecond conformational dynamics do not catalyze the chemical step.

Pisliakov Andrei V AV Cao Jie J Kamerlin Shina C L SC Warshel Arieh A

Proceedings of the National Academy of Sciences of the United States of America 20090925 41

The idea that enzymes catalyze reactions by dynamical coupling between the conformational motions and the chemical coordinates has recently attracted major experimental and theoretical interest. However, experimental studies have not directly established that the conformational motions transfer energy to the chemical coordinate, and simulating enzyme catalysis on the relevant timescales has been impractical. Here, we introduce a renormalization approach that transforms the energetics and dynamic ...[more]

PMID: 19805169

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