(291e) Sampling Time-Resolved Reaction Pathways for Chemical and Biochemical Reactions in Solvent and in Enzyme

Investigating time-resolved reaction pathway is essential for the understanding of chemistry and chemical engineering processes at an atomic level. We developed a sampling method, environment-perturbed transition state sampling (EPTSS), for exploring time-resolved reaction pathways in solvent and in enzyme. The method applies classical molecular dynamics to sample instantaneous configurations of solvent molecules or protein, and then performs multiscale quantum mechanics/molecular mechanics (QM/MM) methods to optimize "environment-perturbed" transition structures. Transition state normal mode sampling is then conducted to gain an ensemble of transition state geometries and momenta, which are used to initiate reaction dynamics trajectories simulations using QM/MM method. The resulting trajectories demonstrate how individual molecules dynamically climb reaction barrier and convert to final product, informing how energy transfer and molecular collisions perturb the reaction pathways and reaction outcomes. The EPTSS method has been applied in water-accelerated Diels-Alder reaction, allylboration of benzaldehyde, and SpnF enzyme-catalyzed Diels-Alder reactions. These studies provide insight into how solvent molecules/proteins dynamically participate in the reaction, and how post-transition state dynamics determines the selectivity of reactions in solvent or enzyme.