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

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.

Automated summary

Native mass spectrometry (nMS) is a biophysical method that allows the analysis of proteins in their native state, providing insights into protein complexes, protein-ligand interactions, and protein-protein interactions (PPIs). It has been increasingly used in early drug discovery for characterizing protein-drug interactions and evaluating PPI modulators. In this article, recent developments in nMS-directed drug discovery and potential applications of this technology in drug discovery are discussed.