title: NMR paves the way for atomic level descriptions of sparsely populated, transiently formed biomolecular conformers.
abstract: The importance of dynamics to biomolecular function is becoming increasingly clear. A description of the structure-function relationship must, therefore, include the role of motion, requiring a shift in paradigm from focus on a single static 3D picture to one where a given biomolecule is considered in terms of an ensemble of interconverting conformers, each with potentially diverse activities. In this Perspective, we describe how recent developments in solution NMR spectroscopy facilitate atomic resolution studies of sparsely populated, transiently formed biomolecular conformations that exchange with the native state. Examples of how this methodology is applied to protein folding and misfolding, ligand binding, and molecular recognition are provided as a means of illustrating both the power of the new techniques and the significant roles that conformationally excited protein states play in biology.
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada M5S 1A8.
authors.forename: Ashok
authors.initials: A
authors.lastname: Sekhar
authors.forename: Lewis E
authors.initials: LE
authors.lastname: Kay
mesh_terms: D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D002147:Calmodulin / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D051076:Proto-Oncogene Proteins c-fyn / Q000737:chemistry / Q000378:metabolism; D015203:Reproducibility of Results; D018909:src Homology Domains
chemical_list: D002147:Calmodulin; D051076:Proto-Oncogene Proteins c-fyn; D002118:Calcium
keywords: energy landscape; invisible states; structure–function paradigm; transiently and sparsely populated biomolecular states