Computational study of structure function and dynamics of biologically relevant molecules in enzymatic reaction

Abstract

Life on earth would not be possible without the catalysis of the biological reaction by the newlineenzymes. Protein biosynthesis is a fundamental enzymatic life process. Aminoacylation newlinereaction is the first step of protein biosynthesis, catalyzed by aminoacyl tRNA synthetase newline(aaRS) in the presence of transfer ribonucleic acid (tRNA). The present thesis focuses on the newlineaminoacyl tRNA synthetase (aaRS) enzyme. The mechanisms of the steps of protein newlinebiosynthesis are studied extensively using various methods, such as crystallographic analysis, newlinewhich provided structural information about the aaRS and tRNA at the various steps of the newlinereaction. Computational studies can provide a detailed molecular understanding of the newlineenzymatic reactions. Present day computational techniques are capable of providing a detailed newlineunderstanding of the interactions controlling the process, how an inhibitor acts in the active newlinesite of enzyme (with a focus on drug design), nature of the stationary points (such as, newlineintermediates, pre-transition state complexes and transition states), stereochemistry of the newlinereaction, charge distribution, electrostatic potential, to mention a few. A major goal of the newlineproposed study is to identify the role of various residues and ions in the active site on the newlineprogress of the reaction mechanism where the substrate, analogue, or inhibitors are present, newlineusing molecular dynamics simulation and quantum mechanical studies. After an introduction newlineabout the present status of knowledge about the subject and methodologies used in the present newlinethesis, classical molecular dynamics simulation and quantum mechanical analysis of class I newlineand class II aaRSs, Glutamyl tRNA synthetase (GluRS), Isoleucyl tRNA synthetase (IleRS) newlineand Seryl tRNA synthetase (SerRS) bound with the cognate substrate and/or inhibitor are newlinepresented in the successive chapters of the thesis. The focus is to understand the structural newlinedetails, conformational dynamics, and function of the active site as well as the enzyme and newlinetRNA.