Linear and non-linear vibrational spectroscopy provides a powerful tool to probe the structure and conformational dynamics of nucleic acids. In the first part of my talk, I will describe our recent progress on the modeling of vibrational spectra of nucleic acids. We have developed vibrational frequency maps and coupling models that allow one to calculate the vibrational Hamiltonian, and thus the vibrational spectra, of nucleic acids in the base carbonyl stretch region directly from MD simulations. Using a set of nucleobase derivatives and oligonucleotides, I will show that the predicted IR spectra in the 1600 – 1800 cm-1 region are in quantitative agreement with the experiment measurements. Our theoretical methods effectively connect MD simulations and spectroscopy experiments, which will provide molecular-level insight into the origin of the observed vibrational spectra of nucleic acids.
Short hydrogen bonds, which have the heteroatom distances below 2.7 Å, occur extensively in organic small molecules and biological macromolecules. In the second part of the talk, I will discuss the structural and chemical features of short hydrogen bonds from our recent statistical analysis of the Protein Data Bank. From electronic structure calculations, we show that short hydrogen bonds in proteins exhibit considerable quantum mechanical characters and share common features in their proton potential energy surfaces. We have further carried out first principles simulations on a set of model molecules that mimic these biological short hydrogen bonds and elucidated how electronic and nuclear quantum effects promote the sharing of the proton in the hydrogen bonds and lead to distinctive 1H NMR chemical shifts. These findings will facilitate the investigation of the structure and functional roles of short hydrogen bonds in biological systems.