Binding of fullerenes to amyloid beta fibrils: size matters

Abstract

Binding affinity of fullerenes C20, C36, C60, C70 and C84 for amyloid beta fibrils is studied by docking and all-atom molecular dynamics simulations with the Amber 99SB force field and water model TIP3P. Using the molecular mechanic-Poisson Boltzmann surface area method one can demonstrate that the binding free energy linearly decreases with the number of carbon atoms of fullerene, i.e. the larger is the fullerene size, the higher is the binding affinity. Overall, fullerenes bind to Aβ_9–40 fibrils stronger than to Aβ_17–42. The number of water molecules trapped in the interior of 12Aβ_9–40 fibrils was found to be lower than inside pentamer 5Aβ_17–42. C60 destroys Aβ_17–42 fibril structure to a greater extent compared to other fullerenes. Our study revealed that the van der Waals interaction dominates over the electrostatic interaction and non-polar residues of amyloid beta peptides play the significant role in interaction with fullerenes providing novel insight into the development of drug candidates against Alzheimer's disease.