title: Protein Allostery and Conformational Dynamics.
abstract: The functions of many proteins are regulated through allostery, whereby effector binding at a distal site changes the functional activity (e.g., substrate binding affinity or catalytic efficiency) at the active site. Most allosteric studies have focused on thermodynamic properties, in particular, substrate binding affinity. Changes in substrate binding affinity by allosteric effectors have generally been thought to be mediated by conformational transitions of the proteins or, alternatively, by changes in the broadness of the free energy basin of the protein conformational state without shifting the basin minimum position. When effector binding changes the free energy landscape of a protein in conformational space, the change affects not only thermodynamic properties but also dynamic properties, including the amplitudes of motions on different time scales and rates of conformational transitions. Here we assess the roles of conformational dynamics in allosteric regulation. Two cases are highlighted where NMR spectroscopy and molecular dynamics simulation have been used as complementary approaches to identify residues possibly involved in allosteric communication. Perspectives on contentious issues, for example, the relationship between picosecond-nanosecond local and microsecond-millisecond conformational exchange dynamics, are presented.
authors.affiliation: School of Chemistry and Chemical Engineering, Henan Normal University , Xinxiang, Henan 453007, People's Republic of China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Physics and Institute of Molecular Biophysics, Florida State University , Tallahassee, Florida 32306, United States.
authors.forename: Huan-Xiang
authors.initials: HX
authors.lastname: Zhou
mesh_terms: D000494:Allosteric Regulation; D020134:Catalytic Domain; D056004:Molecular Dynamics Simulation; D000072340:NIMA-Interacting Peptidylprolyl Isomerase / Q000737:chemistry / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D013816:Thermodynamics
chemical_list: D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D011506:Proteins