کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1951984 1538415 2015 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
α-synuclein dimer structures found from computational simulations
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
α-synuclein dimer structures found from computational simulations
چکیده انگلیسی


• Computational simulations of α-synuclein dimers were performed.
• These simulations gave useful insights regarding the interactions between monomers of α-synuclein.
• Binding energies show that hydrophobic interactions play an important role in binding.
• Interface information obtained may be helpful in pharmacophore modeling.

Dimer 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.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimie - Volume 116, September 2015, Pages 133–140
نویسندگان
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