title: Ion mobility-mass spectrometry of intact protein--ligand complexes for pharmaceutical drug discovery and development.
abstract: Mass spectrometry (MS) plays a number of key roles in the discovery and development phases for modern pharmaceutical compounds, ranging from the assessment of protein-ligand binding to biomarker discovery. Historically, however, MS has had a relatively limited role in the drug discovery process in comparison to high-throughput fluorescence and radiometric screens. This picture may be changing, however, as many presumptive protein targets are coupled to human disease pathways through specific protein-protein interactions and protein conformations, rather than enzyme activities. This fact will likely drive the development of high-throughput analytical tools that put a stronger emphasis on the structural information content produced in a screen. Here we summarize recent developments surrounding ion mobility-mass spectrometry (IM-MS), one such MS-based tool that is capable of rapidly measuring changes in protein structure, oligomeric state, and binding stoichiometry from complex mixtures at relatively low concentrations.
authors.affiliation: Department of Chemistry, University of Michigan, 930 N. University Avenue, Ann Arbor, MI 48109, USA.
authors.forename: Shuai
authors.initials: S
authors.lastname: Niu
authors.forename: Jessica N
authors.initials: JN
authors.lastname: Rabuck
authors.forename: Brandon T
authors.initials: BT
authors.lastname: Ruotolo
mesh_terms: D055808:Drug Discovery; D006801:Humans; D007477:Ions / Q000737:chemistry; D008024:Ligands; D013058:Mass Spectrometry / Q000379:methods*; D055503:Protein Multimerization; D011506:Proteins / Q000737:chemistry*
chemical_list: D007477:Ions; D008024:Ligands; D011506:Proteins