Molecular Simulation For Neurodegenerative Diseases: From Modelling Alpha-Synuclein In Aqueous Solutions To Drug Delivery Systems

<p>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.</p> <p>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 &Aring;, 16.3 &Aring;, 21.7 &Aring; and 27.1 &Aring;, 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.</p>

Name thesis:degree_name

Master of Science (MS)

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

Chemistry

Year

2013

Author dc:creator

• Hicks, Erica Ann

Contributors dc:contributor

• Jerome Delhommelle

• alpha-synuclein, amantadine, Exapanded Wang-Landau, molecular dynamics, single-walled carbon nanotubes

Repository record dc:identifier

https://commons.und.edu/theses/1543

OAI identifier oai:identifier

oai:commons.und.edu:theses-2544