Bioinformatics, Homology Modeling and Parkinson’s Disease
Dr. Owen McDougal
The goal of this study is to combine in silico binding calculations with biological expression experiments of nicotinic acetylcholine receptors (nAChR) in Xenopus oocytes. Nicotinic acetylcholine receptors (nAChRs) are primarily found in neuronal and muscle cells. They are pentameric ligand gated ion channels that can be formed from heteromeric or homomeric subunits. The primary subunit combinations of this study are a6b2 and a3b2. Analog models of a-conotoxin MII have helped to characterize a6b2* containing nAChRs, which are proven to degrade in the brain tissue of Parkinson’s disease patients. Homology modeling was used to create three dimensional structure representations for nAChRs with the desired subunit combinations. In silico binding studies between the a3b2 ligand binding domain of the nAChR and a-conotoxin MII and three analogs were performed. The results showed improved estimation of free binding energy and inhibitory constants compared to that of the acetylcholine binding protein from Aplysia californica, in addition to binding trends that follow suit with in vitro experimental results.