1A-PL-1020 PDF
Using mass spectrometry to study nucleic acid biophysics
Specific nucleic acid structures such as G-quadruplexes (G4) or riboswitches are able to modulate gene expression levels both at the transcriptional and at the translational level. Nucleic acids also serve as building blocks for synthetic nano-assemblies. In all cases, understanding the biophysics of nucleic acid folding requires new techniques to probe the structures adopted by a wide variety of sequences, their macromolecular assemblies, and their interactions with their environment. This presentation will survey native mass spectrometry and ion mobility spectrometry approaches that can be used to probe small molecule (ions or ligands) interactions with G4 structures. We will also describe the fundamental principles underlying correct interpretation of mass spectrometry-derived data for biophysics. First, MS is uniquely well suited to detect and quantify DNA-drug interactions in a direct binding assay. With mass and intensity measurement, one can characterize the binding affinity and specificity of ligands to a variety of targets. We will also highlight how some details, such as cation binding, can also give insight into nucleic acid folding, ligand binding mode, and ligand-induced changes in folding. Finally, ion mobility spectrometry and ion spectroscopy also allow studying the conformational space of the nucleic acids, and ligand-induced conformational changes.