Identifying prospective inhibitors against LdtMt5 from Mycobacterium tuberculosis as a potential drug target.

TL;DR: This chapter discusses tuberculosis through the life cycle of Mycobacterium tuberculosis, followed by a discussion of quantum mechanics/molecular mechanics and its role in the tuberculosis burden.

Abstract: ............................................................................................................................... ii DECLARATION: PLAGIARISM ......................................................................................... iv LIST OF PUBLICATIONS .................................................................................................... ix DEDICATION ........................................................................................................................ x ACKNOWLEDGEMENTS .................................................................................................... xi LIST OF ABBREVIATIONS ................................................................................................ xii LIST OF FIGURES .............................................................................................................. xv LIST OF TABLES ............................................................................................................... xvii Chapter 1 .................................................................................................................................. 18 Introduction .............................................................................................................................. 18 1.0 Background ......................................................................................................................... 18 1.1 Global Tuberculosis burden ................................................................................................ 18 1.1.1 Infection life cycle of Mycobacterium tuberculosis................................................................. 19 1.1.2 Mycobacteria cell wall ............................................................................................................. 20 1.1.2.1 The structural cell wall of Mycobacterium tuberculosis ....................................................... 20 1.1.2.2 Peptidoglycan layer of Mycobacterium tuberculosis ............................................................ 21 1.1.2.3 Transpeptidases and mycobacterial cell wall biosynthesis ................................................... 24 1.1.2.4 Inhibition of L,D Transpeptidase enzymes ........................................................................... 25 1.1.2.5 Computational studies on L,D Transpeptidase enzymes ...................................................... 25 1.2 Computational methods ...................................................................................................... 27 1.2.1 Virtual Screening ..................................................................................................................... 27 1.2.2 Molecular Dynamics (MD) Simulation ................................................................................... 29 1.2.3 Molecular Mechanics (MM) .................................................................................................... 30 1.2.4 Quantum Mechanics (QM) ...................................................................................................... 30 1.2.5 Hybrid quantum mechanics/molecular mechanics (QM/MM) ................................................ 31 1.2.5.1 ONIOM ................................................................................................................................. 32