Native mass spectrometry-directed drug discovery: Recent advances in investigating protein function and modulation

Abstract

Native mass spectrometry (nMS) is a biophysical method for studying protein complexes and can provide insights into subunit stoichiometry and composition, protein-ligand, and protein-protein interactions (PPIs). These analyses are made possible by preserving non-covalent interactions in the gas phase, thereby allowing the analysis of proteins in their native state. Consequently, nMS has been increasingly applied in early drug discovery campaigns for the characterization of protein-drug interactions and the evaluation of PPI modulators. Here, we discuss recent developments in nMS-directed drug discovery and provide a timely perspective on the possible applications of this technology in drug discovery.

Keywords: PROTAC; membrane proteins; native mass spectrometry; protein–ligand interactions; protein–protein interactions.