In this feature article we provide a side-by-side introduction for two research fields quantum chemical calculations of molecular interaction in nucleic acids and RNA structural bioinformatics Our main aim is to demonstrate that these research areas while largely separated in contemporary literature have substantial potential to complement each other that could significantly contribute to our understanding of the exciting world of nucleic acids We identify research questions amenable to the combined application of modern ab initio methods and bioinformatics analysis of experimental structures while also assessing the limitations of these approaches The ultimate aim is to attain valuable physicochemical insights regarding the nature of the fundamental molecular interactions and how they shape RNA structures, dynamics, function, and evolution