How Important Are Quantum Mechanical Nuclear Motions in Enzyme Catalysis?

Abstract

The role of quantum mechanical nuclear motions in enzymatic reactions is examined by realistic simulations that take into account the fluctuations of an entire enzyme−substrate complex. This is done by using the quantized classical path (QCP) approach which is based on Feynman's path integral formulation. The calculations evaluate the quantum mechanical activation free energy and deuterium isotope effect for the proton transfer step in the catalytic reaction of carbonic anhydrase. The calculated and observed isotope effects are in very good agreement, thus demonstrating the potential of our approach in extracting mechanistic information. Furthermore, the value of the calculated quantum mechanical rate constant is in a good agreement with the corresponding observed value. This is significant since the evaluation of the ratio between the quantum mechanical rate constants of the reaction in the protein and in aqueous solution does not involve any adjustable parameter. The reliability of our calculations is b...