title: Folding of the 25 residue Abeta(12-36) peptide in TFE/water: temperature-dependent transition from a funneled free-energy landscape to a rugged one.
abstract: The free-energy landscape of the Alzheimer beta-amyloid peptide Abeta(12-36) in a 40% (v/v) 2,2,2-trifluoroethanol (TFE)/water solution was determined by using multicanonical molecular dynamics simulations. Simulations using this enhanced conformational sampling technique were initiated from a random unfolded polypeptide conformation. Our simulations reliably folded the peptide to the experimental NMR structure, which consists of two linked helices. The shape of the free energy landscape for folding was found to be strongly dependent on temperature: Above 325 K, the overall shape was funnel-like, with the bottom of the funnel coinciding exactly with the NMR structure. Below 325 K, on the other hand, the landscape became increasingly rugged, with the emergence of new conformational clusters connected by low free-energy pathways. Finally, our simulations reveal that water and TFE solvate the polypeptide in different ways: The hydrogen bond formation between TFE and Abeta was enhanced with decreasing temperature, while that between water and Abeta was depressed.
authors: Clinical Genome Informatics Center, Kobe University, Graduate School of Medicine, 1-5-6 Minatojima-Minami-machi, Chuo-ku, Kobe 650-0047, Japan.
authors: Narutoshi
authors: N
authors: Kamiya
authors: Daisuke
authors: D
authors: Mitomo
authors: Joan-Emma
authors: JE
authors: Shea
authors: Junichi
authors: J
authors: Higo
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry*; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry*; D011138:Polytetrafluoroethylene / Q000737:chemistry*; D011487:Protein Conformation; D017510:Protein Folding; D013696:Temperature; D013816:Thermodynamics; D014867:Water / Q000737:chemistry*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C504790:amyloid beta-protein (12-36); D014867:Water; D011138:Polytetrafluoroethylene