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Anders Irbäck. Photo.

Anders Irbäck

Professor

Anders Irbäck. Photo.

Monte Carlo Study of the Formation and Conformational Properties of Dimers of Aβ42 Variants.

Author

  • Simon Mitternacht
  • Iskra Staneva
  • Torleif Härd
  • Anders Irbäck

Summary, in English

Small soluble oligomers, as well as dimers in particular, of the amyloid β-peptide (Aβ) are believed to play an important pathological role in Alzheimer's disease. Here, we investigate the spontaneous dimerization of Aβ42, with 42 residues, by implicit solvent all-atom Monte Carlo simulations, for the wild-type peptide and the mutants F20E, E22G and E22G/I31E. The observed dimers of these variants share many overall conformational characteristics but differ in several aspects at a detailed level. In all four cases, the most common type of secondary structure is intramolecular antiparallel β-sheets. Parallel, in-register β-sheet structure, as in models for Aβ fibrils, is rare. The primary force driving the formation of dimers is hydrophobic attraction. The conformational differences that we do see involve turns centered in the 20-30 region. The probability of finding turns centered in the 25-30 region, where there is a loop in Aβ fibrils, is found to increase upon dimerization and to correlate with experimentally measured rates of fibril formation for the different Aβ42 variants. Our findings hint at reorganization of this part of the molecule as a potentially critical step in Aβ aggregation.

Department/s

  • Computational Biology and Biological Physics
  • MultiPark: Multidisciplinary research focused on Parkinson´s disease

Publishing year

2011

Language

English

Pages

357-367

Publication/Series

Journal of Molecular Biology

Volume

410

Issue

2

Document type

Journal article

Publisher

Elsevier

Topic

  • Biophysics

Keywords

  • protein aggregation
  • amyloid
  • oligomerization
  • molecular simulation
  • all atom

Status

Published

ISBN/ISSN/Other

  • ISSN: 1089-8638