Path Integral-Free Energy Perturbation (PI-FEP) Simulations: Kinetic Isotope Effects of Proton/Deuteron Transfer Reactions in Aqueous Solution.

ABSTRACT: We present a tutorial review of the theoretical background and a step-by-step computational procedure for determining kinetic isotope effects (KIE) of chemical reactions in aqueous solution. The method combines path integral and free energy perturbation (PI-FEP) simulations to directly yield the ratio of the partition functions between different isotopic reactions. This review is the result from a collaborative work in a Computational Chemistry course at the University of Minnesota, where two intramolecular proton transfer reactions were given as classroom exercises. Through this study, we wish to accomplish three main goals: (i) determination of nuclear quantum effects and quantum-mechanical potentials of mean force (QM-PMF), (ii) computation of primary KIE using PI-FEP simulations, and (

SUBMITTER: Gao J 

PROVIDER: S-EPMC12757078 | biostudies-literature | 2025 Nov-Dec

REPOSITORIES: biostudies-literature