A Theoretical Approach to Engineering a New Enzyme

5th International Conference on Mathematical Modeling in Physical Sciences

物理学;数学

Anderson, Greg^1 ; Behera, Raghu N.^2 ; Gomatam, Ravi^1

Bhaktivedanta Institute, Juhu Road, Juhu, Mumbai

400049, India^1

Birla Institute of Technology and Science Pilani, K.K. Birla Goa Campus, Zuarinagar, Goa

403726, India^2

关键词: Artificial enzymes;    Chloroperoxidase;    Density function theory;    Electronic differences;    Natural bond orbital;    Protonation state;    Theoretical approach;    Theoretical calculations;   

Others  :  https://iopscience.iop.org/article/10.1088/1742-6596/738/1/012013/pdf
DOI  :  10.1088/1742-6596/738/1/012013

来源: IOP

【 摘 要 】

Density function theory, a subfield of quantum mechanics (QM), in combination with molecular mechanics (MM) has opened the way to engineer new artificial enzymes. Herein, we report theoretical calculations done using QM/MM to examine whether the regioselectivity and rate of chlorination of the enzyme chloroperoxidase can be improved by replacing the vanadium of this enzyme with niobium through dialysis. Our calculations show that a niobium substituted chloroperoxidase will be able to enter the initial steps of the catalytic cycle for chlorination. Although the protonation state of the niobium substituted enzyme is calculated to be different from than that of the natural vanadium substituted enzyme, our calculations show that the catalytic cycle can still proceed forward. Using natural bond orbitals, we analyse the electronic differences between the niobium substituted enzyme and the natural enzyme. We conclude by briefly examining how good of a model QM/MM provides for understanding the mechanism of catalysis of chloroperoxidase.