The interaction of beta-amyloid (Abeta) peptides with externally applied electric fields (EF) of varying strengths was investigated by means of molecular dynamics (MD) simulations. The results suggest that the EF favors the switch of Abeta-peptides from helical to beta-sheet conformation, and a mechanism is tentatively proposed. Switching off the field does not restore the original conformation.

Amyloid fibrils are highly ordered protein aggregates, which are associated with many neurodegenerative diseases. The assembling dynamics of monomeric beta-amyloid peptides, Aβ, into small aggregates (and then into long fibrils) is still debated and has become a hot topic. In this study, we conducted molecular dynamics simulations in explicit water of small Aβ protofibrils (from monomer to pentamer) under the perturbation of an externally applied electric field with the aim of investigating the fundamental molecular interactions involved in the aggregation mechanism. Dynamics of small adducts of Aβ(16-42) in the presence of an electric field, which was shown before to accelerate the conformational change of a single molecule, indicate that the structural resilience increases with the number of molecules in the aggregate. In particular, for 50 ns, the pentamer shows an enhanced stability in secondary structure, number of hydrogen bonds, and number of salt bridges, even in the presence of the field perturbation. The resilience to the field perturbation is linked to the variation of the induced dipole moment of the aggregates that tends to level off very rapidly with the growing number of molecules, thereby reducing the energy available per molecule to produce structural changes. The results also show that in the presence of the field the stability of the hydrophobic second β-sheet (β2, residues 31-42) is higher than that of the first one (β1, residues 18-26). In particular, we identify Gly33, Gly37, and Met35 as the most important residues that stabilize the intermolecular packing and may act as nucleation sites for fibrillization. Furthermore, dynamics of the full-length Aβ(1-42) pentameric aggregate, which include the highly charged random coil residues 1-15, confirmed the key role of the second hydrophobic core in the protofibril structure.