title: Conformational entropy in molecular recognition by proteins.
abstract: Molecular recognition by proteins is fundamental to almost every biological process, particularly the protein associations underlying cellular signal transduction. Understanding the basis for protein-protein interactions requires the full characterization of the thermodynamics of their association. Historically it has been virtually impossible to experimentally estimate changes in protein conformational entropy, a potentially important component of the free energy of protein association. However, nuclear magnetic resonance spectroscopy has emerged as a powerful tool for characterizing the dynamics of proteins. Here we employ changes in conformational dynamics as a proxy for corresponding changes in conformational entropy. We find that the change in internal dynamics of the protein calmodulin varies significantly on binding a variety of target domains. Surprisingly, the apparent change in the corresponding conformational entropy is linearly related to the change in the overall binding entropy. This indicates that changes in protein conformational entropy can contribute significantly to the free energy of protein-ligand association.
authors.affiliation: Johnson Research Foundation and Department of Biochemistry & Biophysics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Kendra King
authors.initials: KK
authors.lastname: Frederick
authors.forename: Michael S
authors.initials: MS
authors.lastname: Marlow
authors.forename: Kathleen G
authors.initials: KG
authors.lastname: Valentine
authors.forename: A Joshua
authors.initials: AJ
authors.lastname: Wand
mesh_terms: D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002147:Calmodulin / Q000737:chemistry* / Q000378:metabolism*; D019277:Entropy; D006801:Humans; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008745:Methylation; D009068:Movement; D009219:Myosin-Light-Chain Kinase / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D002147:Calmodulin; D008024:Ligands; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; D017346:Protein Serine-Threonine Kinases; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D009219:Myosin-Light-Chain Kinase; D010727:Phosphoric Diester Hydrolases