title: Stability of Osaka Mutant and Wild-Type Fibril Models.
abstract: Single amino acid mutations in amyloid-beta (Aβ) peptides can lead to early onset and increased severity of Alzheimer's disease. An example is the Osaka mutation (Aβ1-40E22D), which is more toxic than wild-type Aβ1-40. This mutant quickly forms early stage fibrils, one of the hallmarks of the disease, and these fibrils can even seed fibrilization of wild-type monomers. Using molecular dynamic simulations, we show that because of formation of various intra- and intermolecular salt bridges the Osaka mutant fibrils are more stable than wild-type fibrils. The mutant fibril also has a wider water channel with increased water flow than the wild type. These two observations can explain the higher toxicity and aggregation rate of the Osaka mutant over the wild type.
authors.affiliation: Department of Chemistry & Biochemistry, University of Oklahoma , Norman, Oklahoma 73019, United States.
authors.forename: Workalemahu M
authors.initials: WM
authors.lastname: Berhanu
authors.affiliation: Department of Chemistry & Biochemistry, University of Oklahoma , Norman, Oklahoma 73019, United States.
authors.forename: Erik J
authors.initials: EJ
authors.lastname: Alred
authors.affiliation: Department of Chemistry & Biochemistry, University of Oklahoma , Norman, Oklahoma 73019, United States.
authors.forename: Ulrich H E
authors.initials: UH
authors.lastname: Hansmann
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000235:genetics; D006860:Hydrogen Bonding; D008958:Models, Molecular; D009154:Mutation; D017433:Protein Structure, Secondary
chemical_list: D016229:Amyloid beta-Peptides