Abstract
Human α‐synuclein (αS) is an intrinsically disordered protein associated with Parkinson's disease. Molecular mechanisms of corruptive misfolding and aggregation of αS resulting in the disease, as well as the structure and other properties of the corresponding oligomers are not entirely understood yet, preventing the development of efficient therapies. In this study, we investigate the folding dynamics of initially unfolded hypothetical αS constructs in water using all‐atom molecular dynamics simulations. We also employ the novel essential collective dynamics method to analyze the results obtained from the simulations. Our comparative analysis of monomeric, dimeric, and tetrameric αS models reveals pronounced differences in their structure and stability, emphasizing the importance of small oligomers, particularly dimers, in the process of misfolding.
Document Type
Article
DOI
https://doi.org/10.1002/2211-5463.12069
Rights Information
© 2016 The Author(s). Published by FEBS Press and John Wiley & Sons Ltd. This is an open access article under a Creative Commons Attribution (CC BY) License.
Keywords
dimers, folding dynamics, molecular dynamics simulations, oligomers, α‐synuclein, β‐sheet‐rich structures
Publication Date
2016
Recommended Citation
Mane, Jonathan Y., and Maria Stepanova. "Understanding the dynamics of monomeric, dimeric, and tetrameric α‐synuclein structures in water." FEBS open bio 6, no. 7 (2016): 666-686.
Journal Title
FEBS Open Bio
