A workflow to define structural classes and classify nucleic acids circular dichroism spectra

Circular dichroism (CD) spectroscopy is a widely utilized technique for studying the structures of chiral molecules, including nucleic acids. It is particularly valued for its ability to quickly probe structural changes in these biomolecules. Despite its potential, the prediction of nucleic acid structures by CD has been challenging due to insufficient families' reference spectral data. This study introduces a robust method for defining CD spectra families of nucleic acid structures. We developed an iterative workflow that accurately classifies spectra for nucleic acid structures in solution. Our approach demonstrates high robustness and accuracy in assigning CD spectra to specific nucleic acid folds, facilitating advancements in nucleic acid structure analysis. The algorithm we developed identifies structural classes based on reference spectra, aiding in the assignment of unknown spectra. This method paves the way for creating a comprehensive list of reference spectra for various nucleic acid structures, like those already available for proteins.