For decades, there has been debate regarding the origin of the catalytic power of enzymes. In this work, we use the approach of computational chemistry to study the enzyme catechol O-methyltransferase (COMT) and reveal that the two current views on the catalytic mechanism of enzymes, the rate-promoting vibrations and the electric field, may both be viewed as part of the chemical step catalyzed by COMT. However, we show that the rate-promoting vibrations cause the electrostatic effect. This work provides insight into the catalytic mechanism of COMT and resolves a long-standing controversy regarding this enzyme's mechanism.
- QM/MM simulation
- electric field preorganization
- rate-promoting vibrations
- transition path sampling
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