Dimer formation enhances structural differences between amyloid β-protein (1-40) and (1-42): an explicit-solvent molecular dynamics study.

ABSTRACT: Amyloid β-protein (Aβ) is central to the pathology of Alzheimer's disease. A 5% difference in the primary structure of the two predominant alloforms, Aβ(1-40) and Aβ(1-42), results in distinct assembly pathways and toxicity properties. Discrete molecular dynamics (DMD) studies of Aβ(1-40) and Aβ(1-42) assembly resulted in alloform-specific oligomer size distributions consistent with experimental findings. Here, a large ensemble of DMD-derived Aβ(1-40) and Aβ(1-42) monomers and dimers was subjected to fully atomistic molecular dynamics (MD) simulations using the OPLS-AA force field combined with two water models, SPCE and TIP3P. The resulting all-atom conformations were slightly larger, less compact, had similar turn and lower β-strand propensities than those predicted by DMD. Fully atomist

SUBMITTER: Barz B 

PROVIDER: S-EPMC3324527 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature