Skip to main content
SLU publication database (SLUpub)
Research article - Peer-reviewed, 2011

Monte Carlo Study of the Formation and Conformational Properties of Dimers of A beta 42 Variants

Mitternacht, Simon; Staneva, Iskra; Härd, Torleif; Irbäck, Anders

Abstract

Small soluble oligomers, and dimers in particular, of the amyloid beta-peptide (A beta) are believed to play an important pathological role in Alzheimer's disease. Here, we investigate the spontaneous dimerization of A beta 42, 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 beta-sheets. Parallel, in-register beta-sheet structure, as in models for A beta 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 A beta fibrils, is found to increase upon dimerization and to correlate with experimentally measured rates of fibril formation for the different A beta 42 variants. Our findings hint at reorganization of this part of the molecule as a potentially critical step in A beta aggregation. (C) 2011 Elsevier Ltd. All rights reserved.

Keywords

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

Published in

Journal of Molecular Biology
2011, Volume: 410, number: 2, pages: 357-367
Publisher: ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD

      SLU Authors

    • Härd, Torleif

      • Department of Molecular Biology, Swedish University of Agricultural Sciences

    UKÄ Subject classification

    Biophysics
    Biochemistry and Molecular Biology

    Publication identifier

    DOI: https://doi.org/10.1016/j.jmb.2011.05.014

    Permanent link to this page (URI)

    https://res.slu.se/id/publ/40819