Comparison of Coarse-Grained and Atomistic-Level Simulations for Aminoacyl-tRNA Synthetases

Abstract

Aminoacyl-tRNA Synthetases are a group of multi-domain enzymes responsible for catalyzing the covalent attachment of an amino acid to its corresponding tRNA forming an aminoacyl-tRNA. A characteristic of AARSs is the large scale conformational changes they undergo during enzymatic activity. These large scale motions alternate the protein back and forth between its unbound inactive state, and its bound active state. The differences between three different simulation types--normal mode analysis (NMA), atomistic-level molecular dynamics (MD) and coarse-grained molecular dynamics simulations (CMD)--were observed. By examining these three methods, the purpose of this study was to determine a more economical yet accurate approach for investigating large, multi-domain proteins like aminoacyl-tRNA synthetases using today's computational tools.