Abstract:
We used all-atom molecular dynamics to investigate the unbinding of Alzheimer’s Abeta
peptides from amyloid fibrils. The peptide unbinding is driven by temperature-induced
structural fluctuations and is thought of as an elementary step in the molecular recycling
occurring between fibrillized and soluble Abeta species. Several conclusions can be
drawn from our data. Early unbinding stages can be observed on the 100 ns timescale,
although complete dissociation is likely to occur on much longer timescale. The
unbinding pathway starts with fraying of β-strands from Abeta fibril. We predict that
most peptide-fibril interactions will be initially lost by the N-terminal of Abeta peptide.
This unbinding scenario can be modified by the specific location of dissociating peptide
on the fibril edge. Our simulations provide new molecular details on the process of
amyloidogenesis linked to Alzheimer’s disease.
