Molecular Tuning of the Nano-Bio Interface: Alpha-Synuclein's Surface Targeting with Doped Carbon Nanostructures

Carbon nanoparticles are becoming promising agents in treating Parkinson's disease (PD) by preventing the folding and aggregation of α-synuclein, i.e., amyloid formation. Herein, for the first time, highly tunable graphene and carbon nanotubes (CNTs) have been doped using biocompatible silicon atoms for preventing Parkinson's disease. In this study, the conformational changes induced by these nanoparticles, the compactness of nanoparticles, the number of hydrogen bonds, the stability of α-synuclein in the presence of nanoparticles, and the interaction energies between α-synuclein and nanoparticles were investigated using microsecond coarse-grained and all-molecular-atom simulations. Although the nanoparticles considered in this study could induce desirable changes in α-synuclein conformations, Si-graphene (silicon-doped graphene) demonstrated the best performance. Si-graphene showed the highest interaction energy with α-synuclein compared to other nanoparticles, induced the most hydrogen bonds, was the least compact, and showed the most unstable α-synuclein conformation, resulting in the highest capability to prevent the folding and aggregation of α-synuclein. Our results displayed that 2D hexagonal structures, such as graphene and Si-graphene, possess better performance than tubular structures in inducing conformational changes in the α-synuclein protein. Furthermore, it was observed that the doping of silicon in graphene and CNT results in better folding and aggregation of α-synuclein prevention. This molecular investigation offers a nanostructure method in PD treatment.