Using native mass spectrometry to inform drug discovery

At the core of nMS is the ability to preserve non-covalent interactions and perform very accurate mass measurements. This ability has enabled advances in structural biology, including the elucidation of protein homogeneity, oligomeric state, sequence variation and the identity of bound ligands. These advances are made possible by preserving proteins in their native state in solution, followed by careful transfer into the gas phase of the mass spectrometer. As a consequence, nMS is finding applications in increasingly diverse research areas such as high-throughput drug screening, the study of amyloid formation and inhibition, the characterisation of antibody-drug conjugates and the elucidation of the interactions of membrane proteins with lipids and therapeutics. This ability to study the influence of small molecule ligand binding on the cascade of protein interactions that underlie many disease states is therefore providing a new paradigm in drug discovery.