IDENTIFYING PROTEIN INHIBITORS OF THE ALPHA SYNUCLEIN PROTEIN IN PARKINSON’S DISEASE USING INSILCO DOCKING STUDIES

Parkinson's disease (PD) is characterized by a gradual decline in dopamine-producing cells and Lewy bodies in the areas of the brain involved with the disease, making it the second most common neurodegenerative disease. The important protein in Lewy bodies is known as α-synuclein and it is abnormally misfolded and built-up within the Lewy bodies which inhibits the functioning of the neurons, causes loss of the chemical dopamine, and creates problems in motor control. The compounds found to interact with α -synuclein that were aimed at blocking the protein aggregation could thus present the opportunity to develop therapeutic drugs for PD. The aim of this study was to discover phytochemicals that have in silico binding affinity to the α-synuclein protein. Six phytocompounds stimovul, curcumin, rutin, piperine, estradurin, and estrophine were tried against α-synuclein using PyRx software. The compounds are listed in order of the Binding energy predicted and Interaction with selected α-synuclein binding region. Out of the compounds tested, rutin had the most negative docking score (−6.4 kcal/mol) followed by estradurin (−5.7 kcal/mol). The other compounds exhibited lower levels of predicted interactions. From these results, rutin and estradurin may be considered early targets for development as inhibitors of aggregation of α-synuclein as they are found to interact favorably with this protein. Molecular docking is not conclusive evidence to confirm activities of anti-aggregation. The molecular dynamics simulation and biochemical aggregation assays, as well as the cytotoxicity studies, and in vivo and in vitro studies will be necessary for their therapeutic potential in PD to be understood.