Amyloid β peptides aggregation in a mixed membrane bilayer: a molecular dynamics study.

The aggregation of amyloid β peptides resulting in neurotoxic oligomers is an important but yet mysterious process in Alzheimer's disease development. Molecular dynamics simulations were performed to investigate the self-assembly of three full-length amyloid peptides in the zwitterionic dipalmitoylphosphatidylcholine and cholesterol mixed lipid bilayer. During the 1000 ns simulation, the residues 1-27 were found to interact preferentially with the lipid-aqueous interface region, while residues 28-42 show an inclination to remain inside the bilayer hydrophobic tail region. The interaction between peptides and lipids has facilitated the association of Aβ peptides. However, the interaction between cholesterol and peptides is inversely correlated with the extent of the peptide-peptide interactions. Our simulation has uncovered the formation of a short segment of parallel β-sheet between two peptide chains. In another chain, the N- and C-termini came close to each other. All the structural transitions indicate that our simulation has caught a glimpse of the complicated peptide oligomerization process. The full understanding of the underlying mechanism still requires further experimental and theoretical studies.