Nuclear quantum effects and kinetic isotope effects in enzyme reactions

Archives of Biochemistry and Biophysics
Alexandra Vardi-KilshtainDan Thomas Major

Abstract

Enzymes are extraordinarily effective catalysts evolved to perform well-defined and highly specific chemical transformations. Studying the nature of rate enhancements and the mechanistic strategies in enzymes is very important, both from a basic scientific point of view, as well as in order to improve rational design of biomimetics. Kinetic isotope effect (KIE) is a very important tool in the study of chemical reactions and has been used extensively in the field of enzymology. Theoretically, the prediction of KIEs in condensed phase environments such as enzymes is challenging due to the need to include nuclear quantum effects (NQEs). Herein we describe recent progress in our group in the development of multi-scale simulation methods for the calculation of NQEs and accurate computation of KIEs. We also describe their application to several enzyme systems. In particular we describe the use of combined quantum mechanics/molecular mechanics (QM/MM) methods in classical and quantum simulations. The development of various novel path-integral methods is reviewed. These methods are tailor suited to enzyme systems, where only a few degrees of freedom involved in the chemistry need to be quantized. The application of the hybrid QM/MM qua...Continue Reading

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Citations

Mar 19, 2016·Angewandte Chemie·Jan Meisner, Johannes Kästner
Jul 29, 2015·Archives of Biochemistry and Biophysics·V Moliner
Aug 5, 2016·Journal of Chemical Theory and Computation·Yaron PshetitskyDan Thomas Major
Nov 7, 2016·Archives of Biochemistry and Biophysics·José R TormosPaul F Fitzpatrick
Mar 30, 2017·Biochemistry·Elizabeth E TrimmerPaul F Fitzpatrick
Aug 19, 2017·Physical Chemistry Chemical Physics : PCCP·Jan MeisnerJohannes Kästner
Feb 2, 2021·The Journal of Physical Chemistry. B·Anil R Mhashal, Dan Thomas Major
Nov 20, 2020·ChemPlusChem·Vlastimil DorčákEmil Paleček
Aug 19, 2017·Journal of the American Chemical Society·Antonio AngelastroRudolf K Allemann

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