title: Amyloid beta-protein monomer structure: a computational and experimental study.
abstract: The structural properties of the Abeta42 peptide, a main constituent of the amyloid plaques formed in Alzheimer's disease, were investigated through a combination of ion-mobility mass spectrometry and theoretical modeling. Replica exchange molecular dynamics simulations using a fully atomic description of the peptide and implicit water solvent were performed on the -3 charge state of the peptide, its preferred state under experimental conditions. Equilibrated structures at 300 K were clustered into three distinct families with similar structural features within a family and with significant root mean square deviations between families. An analysis of secondary structure indicates the Abeta42 peptide conformations are dominated by loops and turns but show some helical structure in the C-terminal hydrophobic tail. A second calculation on Abeta42 in a solvent-free environment yields compact structures turned "inside out" from the solution structures (hydrophobic parts on the outside, polar parts on the inside). Ion mobility experiments on the Abeta42 -3 charge state electrosprayed from solution yield a bimodal arrival time distribution. This distribution can be quantitatively fit using cross-sections from dehydrated forms of the three families of calculated solution structures and the calculated solvent-free family of structures. Implications of the calculations on the early stages of aggregation of Abeta42 are discussed.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Santa Barbara, CA 93106-9501, USA.
authors.forename: Andrij
authors.initials: A
authors.lastname: Baumketner
authors.forename: Summer L
authors.initials: SL
authors.lastname: Bernstein
authors.forename: Thomas
authors.initials: T
authors.lastname: Wyttenbach
authors.forename: Gal
authors.initials: G
authors.lastname: Bitan
authors.forename: David B
authors.initials: DB
authors.lastname: Teplow
authors.forename: Michael T
authors.initials: MT
authors.lastname: Bowers
authors.forename: Joan-Emma
authors.initials: JE
authors.lastname: Shea
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry*; D019295:Computational Biology; D003198:Computer Simulation; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry*; D017433:Protein Structure, Secondary; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)