Computational screening of nanoparticles coupling to Aß40 peptides and fibrils.

ABSTRACT

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, Aß40-cut-peptide, and synthetic inhibitor ligands, in their selective coupling to Aß40 peptides and their fibrils. The simulations reveal that only Aß40-cut-peptide-covered NPs have strong and selective coupling to Aß40 monomers. On the other hand, positive, positive-neutral, Janus, and peptide NPs couple to the beta sheet surfaces of Aß40 fibrils and only the negative-neutral NPs couple to the fibril tips.