Quantum Transition State Theory for proton transfer reactions in enzymes

TL;DR

This paper develops a quantum transition state theory using a path integral approach to explain quantum tunneling effects in enzyme-catalyzed proton transfer reactions, emphasizing temperature dependence and environmental influences.

Contribution

It introduces a quantum transition state theory framework that accounts for environmental interactions and provides quantitative predictions for enzyme reactions involving quantum tunneling.

Findings

Quantum tunneling occurs below a temperature T0 determined by the potential surface.

Environmental friction has minimal impact on reaction rates at room temperature.

Quantum effects are significant only near the transition state, with low-frequency environmental modes having little influence.

Abstract

We consider the role of quantum effects in the transfer of hyrogen-like species in enzyme-catalysed reactions. This study is stimulated by claims that the observed magnitude and temperature dependence of kinetic isotope effects imply that quantum tunneling below the energy barrier associated with the transition state significantly enhances the reaction rate in many enzymes. We use a path integral approach which provides a general framework to understand tunneling in a quantum system which interacts with an environment at non-zero temperature. Here the quantum system is the active site of the enzyme and the environment is the surrounding protein and water. Tunneling well below the barrier only occurs for temperatures less than a temperature $T_0$ which is determined by the curvature of potential energy surface near the top of the barrier. We argue that for most enzymes this temperature is less than room temperature. For physically reasonable parameters quantum transition state theory gives a quantitative description of the temperature dependence and magnitude of kinetic isotope effects for two classes of enzymes which have been claimed to exhibit signatures of quantum tunneling. The only quantum effects are those associated with the transition state, both reflection at the barrier top and tunneling just below the barrier. We establish that the friction due to the environment is weak and only slightly modifies the reaction rate. Furthermore, at room temperature and for typical energy barriers environmental degrees of freedom with frequencies much less than 1000 cm$^{-1}$ do not have a significant effect on quantum corrections to the reaction rate.