A Kinetic View of Enzyme Catalysis from Enhanced Sampling QM/MM Simulations

The rate constants of enzyme-catalyzed reactions (k_cat) are often approximated from the barrier height of the reactive step. We introduce an enhanced sampling QM/MM approach that directly calculates the kinetics of enzymatic reactions, without introducing the transition state theory assumptions, and takes into account the dynamical equilibrium between the reactive and non-reactive conformations of the enzyme:substrate complex. Our computed k_cat values are in order-of-magnitude agreement with the experimental data for two representative enzymatic reactions.