In Silico Designing of an Industrially Sustainable Carbonic Anhydrase Using Molecular Dynamics Simulation

ACS Omega
Sachin Kumar BharatiySaugata Hazra

Abstract

Carbonic anhydrase (CA) is a family of metalloenzymes that has the potential to sequestrate carbon dioxide (CO2) from the environment and reduce pollution. The goal of this study is to apply protein engineering to develop a modified CA enzyme that has both higher stability and activity and hence could be used for industrial purposes. In the current study, we have developed an in silico method to understand the molecular basis behind the stability of CA. We have performed comparative molecular dynamics simulation of two homologous α-CA, one of thermophilic origin (Sulfurihydrogenibium sp.) and its mesophilic counterpart (Neisseria gonorrhoeae), for 100 ns each at 300, 350, 400, and 500 K. Comparing the trajectories of two proteins using different stability-determining factors, we have designed a highly thermostable version of mesophilic α-CA by introducing three mutations (S44R, S139E, and K168R). The designed mutant α-CA maintains conformational stability at high temperatures. This study shows the potential to develop industrially stable variants of enzymes while maintaining high activity.

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Citations

Oct 11, 2017·Journal of Molecular Recognition : JMR·Dong-Ru SunHong-Xing Zhang
Dec 25, 2019·International Journal of Biological Macromolecules·Sourya BhattacharyaSaugata Hazra
Aug 25, 2021·Protein Engineering, Design & Selection : PEDS·Mirfath Sultana MesbahuddinSubha Kalyaanamoorthy
Aug 17, 2018·The Journal of Physical Chemistry. B·Ricardo Parra-CruzAnca Pordea
Nov 6, 2021·Journal of Computational Chemistry·Catrina NguyenMichelle E McCully
Dec 8, 2021·Journal of Biomolecular Structure & Dynamics·Vivek JunghareSaugata Hazra

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Methods Mentioned

BETA
PCA
Circular Dichroism

Software Mentioned

GROMACS
MATLAB
Scwrl4
Xmgrace
Ng
PyMOL
CA
DSSP
COOT
Chimera

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