title: Effects of solvent on the structure of the Alzheimer amyloid-beta(25-35) peptide.
abstract: The free energy landscape for folding of the Alzheimer's amyloid-beta(25-35) peptide is explored using replica exchange molecular dynamics in both pure water and in HFIP/water cosolvent. This amphiphilic peptide is a natural by-product of the Alzheimer's amyloid-beta(1-40) peptide and retains the toxicity of its full-length counterpart as well as the ability to aggregate into beta-sheet-rich fibrils. Our simulations reveal that the peptide preferentially populates a helical structure in apolar organic solvent, while in pure water, the peptide adopts collapsed coil conformations and to a lesser extent beta-hairpin conformations. The beta-hairpin is characterized by a type II' beta-turn involving residues G29 and A30 and two short beta-strands involving residues N27, K28, I31, and I32. The hairpin is stabilized by backbone hydrogen-bonding interactions between residues K28 and I31; S26 and G33; and by side-chain-to-side-chain interactions between N27 and I32. Implications regarding the mechanism of aggregation of this peptide into fibrils and the role of the environment in modulating secondary structure are discussed.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Santa Barbara, California, USA.
authors.forename: Guanghong
authors.initials: G
authors.lastname: Wei
authors.forename: Joan-Emma
authors.initials: JE
authors.lastname: Shea
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000648:ultrastructure*; D001665:Binding Sites; D001923:Brain Chemistry; D003198:Computer Simulation; D006801:Humans; D008956:Models, Chemical; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry* / Q000648:ultrastructure*; D011485:Protein Binding; D011487:Protein Conformation; D012997:Solvents / Q000737:chemistry*; D014867:Water / Q000737:chemistry*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D012997:Solvents; C074636:amyloid beta-protein (25-35); D014867:Water