Catalysis

Can Electric Field be a Descriptor of Catalytic Activity? A Case Study on Chorismate Mutase

Authors

Abstract

The current theoretical perception of enzymatic activity is highly reliant on the determination of activation energy of the reactions which is often calculated using a computational demanding quantum mechanical calculation. 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 a need of time. Here, we propose the electric field (EF) of the enzyme along the reaction axis as a descriptor for the enzymatic activity using an example of Chorismate Mutase in its native and several variants (R90A, R90G, and R90K/C88S). The study shows a linear correlation between the calculated enzymatic EF and enzymatic activity of all complexes. The MD simulations of the Michaelis complex and the transition state analog (TSA) show a stabilizing force on TSA due to the enzymatic EF. The QM/MM and QM-only DFT calculations with the presence of External Electric Field (EEF) oriented along the reaction axis show that the electric can increase the dipole moment of the TS, thereby, stabilizing it and thus lowers the activation energy.

Content

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Supplementary material

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Supporting Information for "Can Electric Field be a Descriptor of Catalytic Activity? A Case Study on Chorismate Mutase
Supporting information contains the energy contribution calculated by MMPBSA calculations, dipole moments and energy values for different variants and coordinates for the QM and QM/MM optimized geometry of RC, TS and PC.