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Understanding the dynamics of monomeric, dimeric, and tetrameric ?-synuclein structures in water.

ABSTRACT: Human ?-synuclein (?S) is an intrinsically disordered protein associated with Parkinson's disease. Molecular mechanisms of corruptive misfolding and aggregation of ?S 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 ?S 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 ?S models reveals pronounced differences in their structure and stability, emphasizing the importance of small oligomers, particularly dimers, in the process of misfolding.

SUBMITTER: Mane JY

PROVIDER: S-EPMC4932447 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Understanding the dynamics of monomeric, dimeric, and tetrameric α-synuclein structures in water.

Mane Jonathan Y JY Stepanova Maria M

FEBS open bio 20160601 7

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 sim ...[more]

PMID: 27398307

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