Spontaneous Self-assembly of Amyloid β (1-40) into Dimers

The self-assembly and fibrillation of amyloid {beta} (A{beta}) proteins is the neuropathological hallmark of Alzheimers disease. However, the molecular mechanism of how disordered monomers assemble into aggregates remains largely unknown. In this work, we characterize the assembly of A{beta} (1-40) monomers into dimers using long-time molecular dynamics simulations. Upon interaction, the monomers undergo conformational transitions, accompanied by change of the structure, leading to the formation of a stable dimer. The dimers are primarily stabilized by interactions in the N-terminal region (residues 5-12), in the central hydrophobic region (residues 16-23), and in the C-terminal region (residues 30-40); with inter-peptide interactions focused around the N- and C- termini. The dimers do not contain long {beta}-strands that are usually found in fibrils.