α-synuclein dimer structures found from computational simulations

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DOIResolve DOI: http://doi.org/10.1016/j.biochi.2015.07.011
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TypeArticle
Journal titleBiochimie
ISSN0300-9084
Volume116
Pages133140
Subjectdocking; molecular dynamics; MMGBSA; Alpha-synuclein; Alzheimers; neurodegenerative disease
AbstractDimer formation is likely the first step in the oligomerization of α-synuclein in Lewy bodies. In order to prevent α-synuclein aggregation, knowledge of the atomistic structures of possible α-synuclein dimers and the interaction affinity between the dimer domains is a necessary prerequisite in the process of rational design of dimerization inhibitors. Using computational methodology, we have investigated several possible α-synuclein dimer structures, focusing on dimers formed from α-helical forms of the protein found when it is membrane-bound, and dimers formed from β-sheet conformations predicted by simulations. Structures and corresponding binding affinities for the interacting monomers in possible α-synuclein dimers, along with properties including the contributions from different interaction energies and the radii of gyration, were found through molecular docking followed by MD simulations and binding-energy calculations. We found that even though α-synuclein is highly charged, hydrophobic contributions play a significant role in stabilizing dimers.
Publication date
PublisherElsevier
LanguageEnglish
AffiliationNational Institute for Nanotechnology; National Research Council Canada
Peer reviewedYes
NPARC number23001717
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Record identifier2352ee5c-9a53-4f65-b27b-377c6a7c8992
Record created2017-03-21
Record modified2017-03-21
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