Modeling the infrared spectra of oligonucleotides and omega-3 fatty acid esters
Creators: name: Jiang, Yaoyukun
Publisher: name: No Publisher Supplied
Year: 2021

description: Nucleic acids and fatty acids both play a critical role in human physiology. Nucleic acids execute and regulate cellular processes such as gene replication, transcription, translation, and genomic stability. Being important constituents of lipid metabolism, omega-3 fatty acids regulate the nervous system, blood pressure, hematic clotting, glucose tolerance, and inflammatory processes. Vibrational spectroscopy, in particular infrared (IR) spectroscopy, has been widely used to probe the three-dimensional structures and conformational dynamics of nucleic acids. IR spectroscopy also provides a rapid and quantitative tool to assess the quality of the omega-3 fatty acid dietary supplements where the fatty acids are usually in the ester form. As commonly used chromophores, the nucleobase C=O and C=C stretch modes and fatty acid ester carbonyl stretch modes exhibit distinct spectral features originated from different hydrogen bonding, nucleobase stacking, and condensed phase environment. However, a direct assignment of the complex experimental spectral features to the underlying structural and dynamical properties can be difficult. On the other hand, molecular dynamics (MD) simulations offer a complementary approach to provide the atomic-level structural and temporal information of nucleic acids and fatty acid esters but it is unclear how to relate this information to the apparent spectral features. To fill the gap between MD simulations and experimental IR spectra, a theoretical strategy directly connecting the information from MD simulations to the observed spectra is highly needed.To predict the IR spectra of nucleic acids and fatty acid esters from MD trajectories, one useful strategy is to apply the mixed quantum/classical approximation. Under this approximation, the vibrational modes within the carbonyl stretch region are described by the vibrational Hamiltonian, where the diagonal terms are the local frequencies of each local mode and off-diagonal terms are the couplings between two local modes. A central task of this dissertation is to establish a theoretical framework to predict the local frequencies and couplings of nucleobase C=O, C=C, and fatty acid ester C=O groups so that the Hamiltonian can be constructed from the MD simulations of nucleic acids and fatty acid esters. For nucleic acids, there were no previous models to predict the frequencies and couplings for nucleobase C=O and C=C stretches. To address this problem, we have developed the first vibrational frequency maps and first transition charge coupling (TCC) models for those chromophores. For fatty acid esters, we have extended the usage of an established ester frequency map and applied the transition dipole coupling model to calculate the Hamiltonian in the vibrational subspace of ester groups.The frequency maps and TCC models, together with our method of treating through-bond interactions, form a complete framework to model the IR spectra of oligonucleotides directly from MD simulations. We then apply the methods to DNA A- and B-form double helices, RNA hairpin tetraloops, and parallel-stranded DNA G-quadruplexes, and our calculated IR spectra can capture most of the features observed in the experimental spectra within the carbonyl stretch region. Based on the comparison between the theoretical and experimental spectra as well as the analysis of the average vibrational Hamiltonian, we are able to dissect the apparent complicated spectral features of these oligonucleotides at the atomic level.