Investigation of Structural and Chemical Perturbations on Structure Function Relationships of Biomolecules Using Computational Approaches

Abstract

Accurate prediction of structures and understanding the underlying mechanism behind the dynamics of newlinebiopolymers are invaluable to understand various biological applications. The structure and dynamics of molecules newlineare related to its function and have major roles in disease biology, gene regulation, and many other cellular pro- newlinecesses. To pave the way towards disease diagnosis, treatment, and faster drug discovery process, it is essential newlineto understand the mechanism behind complex biological processes at the molecular level. Molecular dynam- newlineics (MD) simulations and various enhanced sampling simulations are capable of capturing atomistic details of newlinevarious biological processes such as protein/RNA unfolding, DNA repair mechanism, enzyme kinetics, targeted newlinegene therapy, and membrane transport mechanism. Moreover, molecular simulations provide useful insights to newlineunravel the dynamic nature and thermodynamic stabilities of nucleic acids, proteins, and other complex macro- newlinemolecules. The findings from this study, provide a detailed understanding of the mechanism behind selected newlinebiological phenomena such as urea mediated RNA unfolding, protein unfolding, the role of modified nucleic newlineacids in antisense therapy, and DNA repair mechanism using biomolecular simulation techniques and various newlinetheoretical, computational approaches. Techniques like all-atom MD simulations, thermodynamic integration, newlineand umbrella sampling simulations have been employed to elucidate the molecular-level mechanism of these newlinebiological processes. newlineThe addition of external perturbations to the system of interest is useful to examine the chemical nature, newlinestructural details, and dynamic progress of molecules with respect to time. In the current work, we aim to probe newlinethe structural, energetic, and thermodynamic aspects of various biomolecules such as nucleobases, amino acids, newlineDNA duplexes, chemically modified nucleic acids, and DNA-protein complexes. The main objective of the newlinecurrent work is to understand the effect of chemical and structural