Computational screening of nanoparticles coupling to Aβ40 peptides and fibrils

Blocking the formation, growth, and breaking of amyloid fibrils by synthetic nanosystems could provide a treatment of neurodegenerative diseases. With this in mind, here atomistic molecular dynamics simulations are used to screen for nanoparticles (NPs), covered with different mixtures of ligands, including positively and negatively charged ligands, Aβ40-cut-peptide, and synthetic inhibitor ligands, in their selective coupling to Aβ40 peptides and their fibrils. The simulations reveal that only Aβ40-cut-peptide-covered NPs have strong and selective coupling to Aβ40 monomers. On the other hand, positive, positive-neutral, Janus, and peptide NPs couple to the beta sheet surfaces of Aβ40 fibrils and only the negative-neutral NPs couple to the fibril tips.