title: Protein recognition and selection through conformational and mutually induced fit.
abstract: Protein-protein interactions drive most every biological process, but in many instances the domains mediating recognition are disordered. How specificity in binding is attained in the absence of defined structure contrasts with well-established experimental and theoretical work describing ligand binding to protein. The signaling protein calmodulin presents a unique opportunity to investigate mechanisms for target recognition given that it interacts with several hundred different targets. By advancing coarse-grained computer simulations and experimental techniques, mechanistic insights were gained in defining the pathways leading to recognition and in how target selectivity can be achieved at the molecular level. A model requiring mutually induced conformational changes in both calmodulin and target proteins was necessary and broadly informs how proteins can achieve both high affinity and high specificity.
authors.affiliation: Department of Physics, University of Houston, Houston, TX 77204.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.forename: Pengzhi
authors.initials: P
authors.lastname: Zhang
authors.forename: Laurel
authors.initials: L
authors.lastname: Hoffman
authors.forename: Swarnendu
authors.initials: S
authors.lastname: Tripathi
authors.forename: Dirar
authors.initials: D
authors.lastname: Homouz
authors.forename: Yin
authors.initials: Y
authors.lastname: Liu
authors.forename: M Neal
authors.initials: MN
authors.lastname: Waxham
authors.forename: Margaret S
authors.initials: MS
authors.lastname: Cheung
mesh_terms: D000818:Animals; D054729:Calcium-Calmodulin-Dependent Protein Kinase Type 1 / Q000737:chemistry*; D002147:Calmodulin / Q000737:chemistry*; D008322:Mammals; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D002147:Calmodulin; D010455:Peptides; D054729:Calcium-Calmodulin-Dependent Protein Kinase Type 1
keywords: calmodulin binding target; coarse-grained molecular simulations; conformational flexibility; hydrophobic motif; stopped-flow fluorescence techniques