Computational modeling of infrared spectroscopy for nucleic acids and fatty acids

Linear and two-dimensional infrared (IR) spectroscopy provides powerful tools for probing the structure, dynamics, and interactions of biomolecules. This dissertation focuses on the theoretical modeling of IR spectroscopy to unravel the molecular-level details of DNA duplexes, G-quadruplexes, and omega-3 fatty acids. By integrating molecular dynamics (MD) simulations with spectroscopy modeling methods, this work establishes a robust framework to interpret the vibrational signatures of complex systems under varying environmental conditions.For nucleic acids, this research highlights the sensitivity of IR spectroscopy to hydrogen bonding, base stacking interactions, and solvation effects, particularly in the 1600–1800 cm−1 region. Our computational methods, combined with isotope labeling techniques, enable the disentanglement of overlapping vibrational modes and reveal site-specific structural dynamics of DNA double helices. These approaches are extended to G-quadruplexes, providing insights into their stability and ion-mediated interactions. For omega-3 fatty acids, the study utilized frequency maps and coupling models tailored to ester carbonyl vibrations, elucidating how molecular conformation and packing influence their spectral features.By bridging experimental IR spectroscopy with atomistic MD simulations, this dissertation work achieves quantitative agreement with measured spectra across a range of biomolecular systems. The results demonstrate how structural changes, electrostatic environments, and intermolecular interactions manifest in IR spectra, providing a detailed understanding of biomolecular behavior.This work contributes to advancing computational spectroscopy by offering new tools and methodologies to study complex biomolecular systems. The developed framework is generalizable and paves the way for future investigations of protein-nucleic acid interactions, lipid assemblies, and other biologically relevant complexes, with applications spanning structural biology, biomedical research, and materials science.