title: Understanding the dynamics of monomeric, dimeric, and tetrameric α-synuclein structures in water.
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.
authors.affiliation: Department of Electrical and Computer Engineering University of Alberta Edmonton Canada; National Institute for Nanotechnology National Research Council Canada Edmonton Canada.
authors.forename: Jonathan Y
authors.initials: JY
authors.lastname: Mane
authors.affiliation: Department of Electrical and Computer Engineering University of Alberta Edmonton Canada; National Institute for Nanotechnology National Research Council Canada Edmonton Canada; Department of Physics, Astronomy, and Materials Science Missouri State University Springfield MO USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Stepanova
keywords: dimers; folding dynamics; molecular dynamics simulations; oligomers; α‐synuclein; β‐sheet‐rich structures