SIMULATIONS OF QUANTUM-MECHANICAL CORRECTIONS FOR RATE CONSTANTS OF HYDRIDE-TRANSFER REACTIONS IN ENZYMES AND SOLUTIONS

A practical approach for simulating quantum mechanical corrections for rate constants of enzymatic reactions is presented. This approach is based on a combination of the dispersed polaron model and a centroid path integral treatment. The quantized activation free energy is conveniently obtained by propagating classical trajectories on the classical potential surface while using the free particle distribution to evaluate the relevant quantum correction. The method is used in a preliminary study of the hydride-transfer step in the catalytic reaction of lactate dehydrogenase (LDH). The isotope effect for this step is evaluated and the relationship between the quantum corrections for the reaction in the enzyme and in a reference solvent cage is examined.