Using Computational Methods to Identify Ligands Capable of Promoting the Disaggregation of Lewy Bodies

Joseph M. Lamson
Dr. Bill Miller (ATSU) and Dr. Andrew Kauffmann, Faculty Mentors

Parkinson’s disease is a neurodegenerative condition resulting from the death of dopaminergic neurons, affecting more than 10 million people.  Symptoms include loss of motor control and cognitive impairment.  The disease has no single cause, but is associated with Lewy bodies.  These are aggregates formed from misfolded α-synuclein proteins, which when folded properly are important to neuronal function.  The purpose of this study is to use computational methods to identify ligands capable of promoting the disaggregation of Lewy bodies.  Approximately 2.3 million ligand structures were downloaded from the ZINC15 database.  These were docked to an α-synuclein aggregate using Qvina, and their binding energies were calculated.  Five of the ligands with the strongest binding were simulated interacting with the aggregate using molecular dynamics.  These simulations were evaluated to determine each ligand’s ability to disrupt α-synuclein aggregation, and the results could prove useful in the search for a drug to treat Parkinson’s disease.  

Keywords: Parkinson's disease, Computational chemistry, Lewy bodies, Qvina, Molecular dynamics

Topic(s):Biochemistry and Molecular Biology
Chemistry

Presentation Type: Oral Presentation

Session: TBA
Location: TBA
Time: TBA