Improving Alpha-Synuclein Aggregation Inhibitors for Parkinson’s Disease Using Computational Chemistry Methods

David Thompson
Dr. Bill R. Miller, Faculty Mentor

Parkinson’s disease is a progressive neurodegenerative disease, causing a variety of motor symptoms such as bradykinesia and tremors as well as non-motor symptoms like insomnia and emotional apathy. Lewy bodies are markers of Parkinson’s and the protein alpha-synuclein has been identified as an important structural component of Lewy bodies. Previous research has identified inhibitors that bind to alpha-synuclein fibrils and break up Lewy bodies as a result. Previously researched inhibitors were selected and their binding to alpha-synuclein fibrils was simulated using molecular dynamics. Free energy calculations and structural analysis were then used to rank each inhibitor and determine specific residue interactions that contribute to the binding of the inhibitor to alpha-synuclein. From this information, structural changes were made to these inhibitors to improve their ability to bind and prevent alpha-synuclein fibril formation in hopes of finding a better drug to treat Parkinson's disease.

Keywords: 

Topic(s):Biochemistry and Molecular Biology
Chemistry

Presentation Type: Oral Presentation

Session: TBA
Location: TBA
Time: TBA