title: Conformational entropy of intrinsically disordered protein.
abstract: Intrinsically disordered proteins (IDPs), though lacking stable tertiary structures, are known to possess a certain amount of residual structure. Conformational disorder plays a crucial role through the conformational entropy in regulating protein-protein and protein-ligand interactions involved in signaling and regulation, and also modulates protein aggregation and amyloidogenesis associated with a number of human diseases. However, a direct and quantitative connection between the residual structure and the conformational entropy remains to be established. Here we show using a novel computational approach that the conformational entropy of amyloid-beta protein, an IDP whose aggregation is associated with Alzheimer's disease, is significantly correlated with the contents of the residual helical structure, β-sheet structure, and salt-bridge network. Identification of the thermodynamically significant residual structure is of fundamental importance for a comprehensive understanding of the relationship between the functional conformational disorder and the protein activity regulation, and will also serve the thermodynamic basis of the amyloid polymorphism.
authors.affiliation: Department of Chemistry, Sookmyung Women's University, Yongsan-Ku, Seoul, Korea.
authors.forename: Song-Ho
authors.initials: SH
authors.lastname: Chong
authors.forename: Sihyun
authors.initials: S
authors.lastname: Ham
mesh_terms: D019277:Entropy; D064267:Intrinsically Disordered Proteins / Q000737:chemistry*; D008958:Models, Molecular; D011487:Protein Conformation
chemical_list: D064267:Intrinsically Disordered Proteins