Traversing the drug discovery landscape using native mass spectrometry

As health needs in our society evolve, the field of drug discovery must undergo constant innovation and improvement to identify novel targets and drug candidates. Owing to its ability to simultaneously capture biological interactions and provide in-depth molecular characterisation of the species involved, native mass spectrometry is starting to play an important role in this endeavour. Here, we discuss recent contributions that native mass spectrometry has made to drug discovery including deciphering protein-small molecule interactions, unravelling biochemical pathways, and integrating with complementary structural approaches. • Unravelling the modulation of biochemical pathways by drug candidates. • Characterising target-small molecule interactions on rapid timescales. • Capturing desirable and off-target ligand binding in native environments. • Defining proteoform selectivity of small molecule ligands.