Computational Study of ɑ-Synuclein Structure and Druggability
Mark A. Healey · ERA: Education and Research Archive (University of Alberta) · 2016
α-Synuclein has been implicated in the progression of Parkinson’s disease, a neurodegenerative disorder that affects millions of people worldwide. This work reports on the structural propensity and druggability of this protein using a combination of Monte Carlo, Molecular Dynamics, and Virtual Screening simulation methods. In performing Monte Carlo simulations, we analysed the extended secondary structure formation for Wild-Type and Mutant α-synuclein above and below the apparent phase transition temperature. We also used the low energy phase of our simulations to approximate the potential compact structures that the protein may exhibit in aggregates. From these results, we were able to determine regions of the protein which exhibit variable extended beta sheet structure, suggesting a possible role in the aggregation of α-synuclein, as well as a number of drugs which hold the potential to bind and inhibit this aggregation.