An Exploration of Molecular Recognition Mechanisms and Ligand Induced Transitions in Biomolecules

Abstract

Molecular recognition refers to processes through which biological macromolecules interact with each other or other small molecules through noncovalent interactions to form specific complexes. Applying molecular recognition principles can aid in developing new drugs, particularly new antimicrobial drugs. Drug development also requires considering the effects of physicochemical factors ( ionic environment, temperature, pressure, co-solvents, and pH) on biomolecular folding and cognate ligand binding mechanisms. Therefore, a detailed understanding of the target–ligand interactions is central to understanding biology at the molecular level. In this thesis, using molecular dynamics simulations, I will be discussing the molecular mechanisms by which non-coding RNA molecules (riboswitches) sense their cognate ligands. I will also be discussing the role of biomolecular excited states on the ligand binding mechanisms of riboswitches. Furthermore, I will discuss the role of physico-chemical factors, namely pH, on the binding kinetics of a target-ligand complex. Finally, I will discuss how mutations in biomolecules can be used to trigger the same response generated by ligand binding.