I present a new method, solvent/enzyme-perturbed transition state sampling (S/EPTSS), to compute energetics and reactive trajectories for reactions in solvent and in enzyme. The method employs classical molecular dynamics (MD) to sample snapshots of solvent molecules or protein residues. Quantum mechanics/molecular mechanics (QM/MM) calculations are performed to optimize transition structures/reactants in the snapshots and to compute free energies by averaging. Reactive trajectories are initiated from these solvent/enzyme-perturbed transition structures based on normal mode sampling. The method has been benchmarked against experimental data for the SpnF-catalyzed Diels-Alder reaction, chorismate mutase-catalyzed Claisen-rearrangement reaction, as well as reactions in water, including Claisen rearrangement, and intramolecular Diels-Alder reactions.

Solvent/enzyme-perturbed transition state sampling and its applications

253rd National Meeting (2017)

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