title: Native Mass Spectrometry in Fragment-Based Drug Discovery.
abstract: The advent of native mass spectrometry (MS) in 1990 led to the development of new mass spectrometry instrumentation and methodologies for the analysis of noncovalent protein-ligand complexes. Native MS has matured to become a fast, simple, highly sensitive and automatable technique with well-established utility for fragment-based drug discovery (FBDD). Native MS has the capability to directly detect weak ligand binding to proteins, to determine stoichiometry, relative or absolute binding affinities and specificities. Native MS can be used to delineate ligand-binding sites, to elucidate mechanisms of cooperativity and to study the thermodynamics of binding. This review highlights key attributes of native MS for FBDD campaigns.
authors.affiliation: Eskitis Institute for Drug Discovery, Griffith University, Brisbane 4111, Queensland, Australia. liliana.pedro@griffithuni.edu.au.
authors.forename: Liliana
authors.initials: L
authors.lastname: Pedro
authors.affiliation: Eskitis Institute for Drug Discovery, Griffith University, Brisbane 4111, Queensland, Australia. r.quinn@griffith.edu.au.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Quinn
mesh_terms: D001665:Binding Sites; D055808:Drug Discovery / Q000379:methods*; D008024:Ligands; D013058:Mass Spectrometry / Q000295:instrumentation / Q000379:methods*; D008958:Models, Molecular; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D054852:Small Molecule Libraries / Q000494:pharmacology*; D013816:Thermodynamics
chemical_list: D008024:Ligands; D011506:Proteins; D054852:Small Molecule Libraries
keywords: binding affinity; binding specificity; binding stoichiometry; fragment-based drug discovery; fragment-based screening; native MS; noncovalent interaction; protein-ligand complex; structure-activity relationship