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  Transient secondary and tertiary structure formation kinetics in the intrinsically disordered state of α-Synuclein from atomistic simulations.

Graen, T., Klement, R., Grupi, A., Haas, E., & Grubmüller, H. (2018). Transient secondary and tertiary structure formation kinetics in the intrinsically disordered state of α-Synuclein from atomistic simulations. ChemPhysChem, 19(19), 2507-2511. doi:10.1002/cphc.201800504.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0001-DB29-B Version Permalink: http://hdl.handle.net/21.11116/0000-0002-5132-A
Genre: Journal Article

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 Creators:
Graen, T.1, Author              
Klement, R.1, Author              
Grupi, A., Author
Haas, E., Author
Grubmüller, H.1, Author              
Affiliations:
1Department of Theoretical and Computational Biophysics, MPI for biophysical chemistry, Max Planck Society, ou_578631              

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Free keywords: alpha-synuclein; intrinsically disordered protein; molecular dynamics; protein models; structural dynamics
 Abstract: In the absence of a stable fold, transient secondary structure kinetics define the native state of the prototypical and pharmacologically relevant intrinsically disordered protein (IDP) α-Synuclein (aS). Here, we investigate kinetics preventing ordering and possibly pathogenic β-sheet aggregation. Interestingly, transient β-sheets form frequently at sub μs time scales precisely at the positions observed in aS amyloid fibrils. The formation kinetics competes with rapid secondary structure dissociation rates, thus explaining the low secondary structure content. The fast secondary structure dissociation times are very similar to the dynamics of tertiary structure rearrangements. These findings suggest that the fast dissociation kinetics slows down conformational selection processes for aS aggregation, which may be a general mechanism controlling the aggregation kinetics of IDPs.

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Language(s): eng - English
 Dates: 2018-07-252018-10-05
 Publication Status: Published in print
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 Rev. Method: Peer
 Identifiers: DOI: 10.1002/cphc.201800504
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Title: ChemPhysChem
Source Genre: Journal
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Pages: - Volume / Issue: 19 (19) Sequence Number: - Start / End Page: 2507 - 2511 Identifier: -