Hydrogen Tunnelling and Enzyme Catalysis

Hydrogen motion, H+, H or H, is often involved in the rate-limiting step of many enzyme catalysed reactions. Here, QM tunnelling can be important and is reflected in the values of the measured kinetic isotope effects (KIEs) [75], Enzyme motion 

The rate of hydrogen transfer can be calculated using the direct dynamics approach of Truhlar and co-workers which combines canonical variational transition state theory (CVT) [82, 83] with semi-classical multidimensional tunnelling corrections [84], The rate constant is calculated using [83]  

The use of Eq. (5-10) to evaluate the reaction rate is characterised by the calculation of Hessians for a large number of points along the MEP which are required to locate the free energy maximum and also to evaluate the curvature required for evaluation of the transmission coefficient. In view of the associated computational expense, high-level electronic structure calculations are not feasible and alternative strategies, one of which is to use a semi-empirical method, are usually employed [81]. 

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