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Permanent link (DOI): https://doi.org/10.7939/R34M91N0N

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Computational Study of ɑ-Synuclein Structure and Druggability Open Access

Descriptions

Other title
Subject/Keyword
Parkinson's Disease
protein
druggability
biophysics
simulation
synuclein
intrinsically disordered protein
monte carlo
molecular dynamics
pulling simulations
Type of item
Thesis
Degree grantor
University of Alberta
Author or creator
Healey, Mark A
Supervisor and department
Tuszynski, Jack (Oncology)
Examining committee member and department
Woodside, Michael (Physics)
Petersen, Nils (Chemistry)
Klobukowski, Mariusz (Chemistry)
Brown, Alex (Chemistry)
Weaver, Donald (University of Toronto, Chemistry)
Department
Department of Physics
Specialization

Date accepted
2016-09-26T07:54:38Z
Graduation date
2016-06:Fall 2016
Degree
Doctor of Philosophy
Degree level
Doctoral
Abstract
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.
Language
English
DOI
doi:10.7939/R34M91N0N
Rights
This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for the purpose of private, scholarly or scientific research. 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.
Citation for previous publication
"Phase Transitions and Structure Analysis in Wild-Type, A30P, E46K, and A53T Mutants of ɑ-Synuclein". MA Healey, M Woodside, and JA Tuszynski. European Biophysics Journal, Dec. 2015.

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