Computational Study of ɑ-Synuclein Structure and Druggability

• Author / Creator

  Healey, Mark A

• 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.

• Subjects / Keywords

  • Proteins
  • Intrinsically disordered protein
  • Parkinson's Disease
  • Druggability
  • Simulations
  • Biophysics
  • Molecular-dynamics
  • Synuclein
  • Monte carlo
  • Pulling simulations

• Graduation date

  Fall 2016

• Type of Item

  Thesis

• Degree

  Doctor of Philosophy

• DOI

  https://doi.org/10.7939/R34M91N0N

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.