Molecular simulation for neurodegenerative diseases: From modelling alpha-synuclein in aqueous solutions to drug delivery systems

Using computer simulations, we developed a better understanding of some key chemical steps of alpha-synuclein aggregation as well as amantadine for drug delivery systems. The aggregation and fibrillation of alpha-synuclein, a brain protein of 140 residues, has been linked to several neurodegenerative diseases, including Parkinson's and Alzheimer's diseases. Using molecular dynamics, alpha-synuclein, at various temperatures of 293 K, 310 K, 323 K and 348 K, was shown to undergo rapid conformational change. The non-amyloid-beta component (NAC) of alpha-synuclein that is not sterically hindered is suspected to undergo aggregation.;Amantadine has been shown to help regulate the symptoms of Parkinson's disease, and single-walled carbon nanotubes (SWCNs) could be a potential drug carrier. Adsorption of amantadine within SWCNs, at differing diameters of 10.9 A, 16.3 A, 21.7 A and 27.1 A, was studied using Expanded Wang-Landau (EWL) simulations. It was shown that increasing the diameters of the SWCNs increased amantadine loading - monolayers formed for the two smaller SWCNs while bilayers formed for the larger. The diffusion process was studied through molecular dynamics. For the larger two SWCNs, there was a dramatic decrease in the rate of self-diffusion with respect to increasing amantadine loading followed by a moderate decrease. This was attributed to the transition from a monolayer to a bilayer structure.