▎ 摘　　要

Human islet amyloid polypeptide (hIAPP)is the major componentof the amyloid deposited in the pancreas of patients with type 2 diabetesmellitus. Its aggregation and consequent production of intermediatesare believed to be responsible for its cytotoxicity and pathologicalprocesses. Recently, graphene quantum dots (GQDs) are proved to effectivelyinhibit a range of amyloid deposits. This work focuses on the influenceof the charged GQDs on hIAPP inhibition. Microsecond all-atom moleculardynamics simulations in explicit water were performed to study theinfluence of charged GQDs on the structural stability of hIAPP fibril.GQDs were found to be able to destabilize the hIAPP fibril and reducethe beta-sheet content. The stability of the hydrophobic core wasgreatly disturbed, and the hydrogen bond formation at protofibrilinterfaces was also hindered. The negatively and positively chargedGQDs have different binding sites, dynamics, and interactions at hIAPPfibril, which is dominated by electrostatic interaction and assistedby pi-pi stacking, salt bridge, and hydrogen bondinginteractions. The pi-pi stacking between GQDs andhIAPP may be influenced by the electrostatic interaction in a facilitativeor competitive manner. In addition, the negatively charged GQD issuggested to be a better candidate of amyloid inhibition than thepositively charged one in disruptive effect, binding modes, and bindingintensity. These findings may provide useful perspectives for thedesign of nanomedicine for amyloid inhibition and are helpful to thedevelopment of diagnosis and screening nanotechnology for neurodegenerativediseases.