Abstract
This thesis emphasizes mechanism elucidation and structure-based drug design for multiple biological systems. Three main topics investigated are: (1) determining the origin of product specificity for protein arginine methyltransferase 7 (PRMT7) (2) rationalizing the plausible mechanism for mobile loop conformation changes of alkanesulfonate monooxygenase (SsuD) (3) structure-based drug design and determining the structure-activity relationship for curcumin based pyrazoline derivatives targeting monoamine oxidase-A (MAO-A).
Chapter 1 entrails detailed background about biological systems that are investigated to understand their functions (PRMT7 and SsuD) or as targets (MAO-A) for designing specific inhibitors. Chapter 2 describes a detailed theoretical background adopted to computationally investigate the biological systems. Chapter 3 discusses the results obtained from molecular dynamics (MD) and mixed quantum and molecular mechanics coupled with MD simulation to predict the origin of product specificity for PRMT7 enzyme. Chapter 4 based on accelerated molecular dynamics explains the proposed “door” mechanism allowing the conformation changes of mobile loop during sulfur catalysis in SsuD system. Chapter 5 is mainly concern with designing curcumin based pyrazoline inhibitors for MAO-A and rationalizing the structure-activity relationship.