کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1951984 | 1538415 | 2015 | 8 صفحه PDF | دانلود رایگان |

• 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.
Figure optionsDownload high-quality image (94 K)Download as PowerPoint slide
Journal: Biochimie - Volume 116, September 2015, Pages 133–140