Issue 4, 2022

Can the local electric field be a descriptor of catalytic activity? A case study on chorismate mutase

Abstract

The current theoretical perception of enzymatic activity is highly reliant on the determination of the activation energy of the reactions, which is often calculated using computationally demanding quantum mechanical calculations. With the ever-increasing use of bioengineering techniques that produce too many variants of the same enzyme, a fast and accurate way to study the relative efficiency of enzymes is currently in high demand. Here, we propose the local electric field (LEF) of the enzyme along the reaction axis as a descriptor for the enzymatic activity using the example of chorismate mutase in its native form and several variants (R90A, R90G, and R90K/C88S). The study shows a direct correlation between the calculated enzymatic EF and the enzymatic activity for all the complexes. MD simulations of the Michaelis complex and the transition state analog (TSA) show a stabilizing force on the TSA due to the enzymatic EF. QM/MM and QM-only DFT calculations in the presence of an external electric field (EEF) oriented along the reaction axis show that the electric field can interact with the dipole moment of the TS, thereby stabilizing it and thus lowering the activation energy.

Graphical abstract: Can the local electric field be a descriptor of catalytic activity? A case study on chorismate mutase

Supplementary files

Article information

Article type
Paper
Submitted
30 Aug 2021
Accepted
22 Okt 2021
First published
22 Okt 2021

Phys. Chem. Chem. Phys., 2022,24, 1974-1981

Can the local electric field be a descriptor of catalytic activity? A case study on chorismate mutase

S. A. Siddiqui and K. D. Dubey, Phys. Chem. Chem. Phys., 2022, 24, 1974 DOI: 10.1039/D1CP03978D

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