3 years ago

Molecular Dynamics Study to Investigate the Dimeric Structure of the Full-Length α-Synuclein in Aqueous Solution

Molecular Dynamics Study to Investigate the Dimeric Structure of the Full-Length α-Synuclein in Aqueous Solution
Jiajie Zhang, Zichao Yang, Siming Liu, Zhonghuang Li, Yuanxin Tian, Xiang Hu, Shuwen Liu, Xiaotong Ling, Tingting Zhang
The mechanisms of dimerization of α-synuclein from full-length monomers and their structural features have been investigated through molecular dynamics simulations in this study. The dimerization of α-syn plays a critical role in the fibrillogenesis mechanism and could initiate and trigger α-syn to aggregate by conformational transforming. According to the alignment between three regions of α-syn monomer, eight diverse starting structures have been constructed. However, only five configurations show the dimeric structures, and the detailed properties of three dimers of them are discussed. During the simulations, both identical α-syn peptides (P1 and P2) of these three dimers reduce the high contents of α-helix from their native folded structures, while the contents of β-sheet increase. Antiparallel β-hairpin motifs within the α-syn peptide are formed by intramolecular interactions. The β-hairpin regions are adjacent to the nonamyloid β component (NAC) of α-syn, and these structural features are consistent with the experimental observation. Moreover, intermolecular β-sheets also are generated between P1 and P2 through hydrogen bonding interactions. The dimers produce both intramolecular β-hairpin and intermolecular β-sheet characters; the former is presented in monomer and oligomer of α-syn, and the latter occurs in the fibril structure. The simulations also show several other interactions such as hydrophobic interactions and salt-bridges, which would contribute to making the α-syn dimers more stable with the aforementioned effects. The results may pave the way to design small molecules to inhibit the dimerization in order to block the aggregation of α-syn in the future.

Publisher URL: http://dx.doi.org/10.1021/acs.jcim.7b00210

DOI: 10.1021/acs.jcim.7b00210

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.