title: Targeting conformational plasticity of protein kinases.
abstract: The quest for ever more selective kinase inhibitors as potential future drugs has yielded a large repertoire of chemical probes that are selective for specific kinase conformations. These probes have been useful tools to obtain structural snapshots of kinase conformational plasticity. Similarly, kinetic and thermodynamic inhibitor binding experiments provide glimpses at the time scales and energetics of conformational interconversions. These experimental insights are complemented by computational predictions of conformational energy landscapes and simulations of conformational transitions and of the process of inhibitors binding to the protein kinase domain. A picture emerges in which highly selective inhibitors capitalize on the dynamic nature of kinases.
authors.affiliation: Department of Pharmacological Sciences, Stony Brook University , Stony Brook, New York 11794, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Tong
authors.forename: Markus A
authors.initials: MA
authors.lastname: Seeliger
mesh_terms: D000818:Animals; D019295:Computational Biology; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D011494:Protein Kinases / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D008024:Ligands; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases