Exploring the Interplay of Dynamics and Catalysis in Escherichia coli Prolyl-tRNA Synthetase using Quantum Mechanical/Molecular Mechanical Simulations

Abstract

The intrinsic dynamics that are inherent in proteins are known to be critical for many important biochemical processes. However, there is still limited information regarding how dynamics favor enzymes to achieve their enormous rate enhancement. To better understand the molecular mechanism of the interplay between dynamics and catalysis, we attempted to model an important biochemical reaction known as prolyl-adenylate formation. This reaction is catalyzed by prolyl-tRNA synthetase, a member of the family of aminoacyl-tRNA synthetases. We have used quantum mechanical/molecular mechanical (QM/MM) approaches to model and compute energetics of the adenylate formation reaction in enzyme and enzyme-free (aqueous) system. Herein, we have presented the preliminary results, which include the free-energy of activation of prolyladenylate formation for the wild type and mutant enzymes.