Carbon nanotube prevents the secondary structure formation of amyloid-β trimers: an all-atom molecular dynamics study

Increasing evidence shows that the formation of misfolded aggregates amyloid-beta (A beta) peptide is associated with the Alzheimer's disease (AD). Recent experiments reveal a significant correlation of the amount of trimer species bound to neurons with increasing neuro-toxicity. Our previous computational study demonstrated that carbon nanotubes (CNT) can inhibit effectively the formation of beta-sheet-rich oligomers of A beta(16-22) - a hydrophobic peptide essential for A beta fibrillization. However, the influence of CNT on the oligomers formed by full-length A beta remains elusive. In this study, we have investigated the conformational dynamics of A beta(1-42) trimer, built from an NMR structure of a-helical monomer, in the absence and presence of a single-walled carbon nanotube (SWCNT). Our simulations demonstrate that SWCNT can significantly hinder the trimerisation and prevents the secondary structure formation of A beta(1-42) peptide. Hydrophobic and aromatic stacking interactions between SWCNT and A beta play important roles in the secondary structure formation of the A beta trimer. This study reveals a complete picture of the detailed preventable mechanism of full-length A beta(1-42) by SWCNT, providing theoretical insights into the development of drug candidates of AD.