title: Allostery in disease and in drug discovery.
abstract: Allostery is largely associated with conformational and functional transitions in individual proteins. This concept can be extended to consider the impact of conformational perturbations on cellular function and disease states. Here, we clarify the concept of allostery and how it controls physiological activities. We focus on the challenging questions of how allostery can both cause disease and contribute to development of new therapeutics. We aim to increase the awareness of the linkage between disease symptoms on the cellular level and specific aberrant allosteric actions on the molecular level and to emphasize the potential of allosteric drugs in innovative therapies.
authors.affiliation: National Cancer Institute, Center for Cancer Research Nanobiology Program, Frederick National Laboratory for Cancer Research, SAIC-Frederick, Inc., National Cancer Institute, Frederick, MD 21702, USA. nussinor@helix.nih.gov
authors.forename: Ruth
authors.initials: R
authors.lastname: Nussinov
authors.forename: Chung-Jung
authors.initials: CJ
authors.lastname: Tsai
mesh_terms: D000494:Allosteric Regulation; D000495:Allosteric Site; D000818:Animals; D004194:Disease / Q000235:genetics*; D055808:Drug Discovery; D004358:Drug Therapy; D004798:Enzymes; D006801:Humans; D008958:Models, Molecular; D011487:Protein Conformation; D047428:Protein Kinase Inhibitors / Q000737:chemistry; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics; D015398:Signal Transduction; D013816:Thermodynamics
chemical_list: D004798:Enzymes; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases