Biophysical assays to test target structure and ligand binding stoichiometry, affinity, specificity and binding modes are part of the drug development pipeline. Mass spectrometry offers unique advantages as a biophysical method due to its ability to distinguish each stoichiometry present in a mixture. In addition, advanced mass spectrometry approaches (reactive probing, fragmentation techniques, ion mobility spectrometry, ion spectroscopy) provide more detailed information on the complexes.
Previous work: This has been a key topic of the Gabelica group for over 20 years, summarized in a comprehensive review of fundamentals of mass spectrometry and all its particularities when studying non-covalent nucleic acid structures. We also reviewed what has been learned thanks to mass spectrometry on nucleic acid structures, self-assemblies (e.g., duplexes or G-quadruplexes), and their complexes with ligands [1]. New projects are outlined below.