Exploring the Aggregation Free Energy Landscape of the Amyloid-β Protein (1-40)

doi:10.1073/pnas.1612362113

淡江大學機構典藏 > 理學院 > 化學學系暨研究所 > 期刊論文 > Item 987654321/117164

請使用永久網址來引用或連結此文件: https://tkuir.lib.tku.edu.tw/dspace/handle/987654321/117164

題名:	Exploring the Aggregation Free Energy Landscape of the Amyloid-β Protein (1-40)
作者:	Zheng, Weihua;Tsai, Min-Yeh;Chen, Mingchen;Wolynes, Peter G
關鍵詞:	amyloid funnel;misfolding;nucleation
日期:	2016-10-18
上傳時間:	2019-09-27 12:11:16 (UTC+8)
出版者:	National Academy of Sciences
摘要:	A predictive coarse-grained protein force field [associative memory, water-mediated, structure, and energy model for molecular dynamics (AWSEM)-MD] is used to study the energy landscapes and relative stabilities of amyloid-β protein (1-40) in the monomer and all of its oligomeric forms up to an octamer. We find that an isolated monomer is mainly disordered with a short α-helix formed at the central hydrophobic core region (L17-D23). A less stable hairpin structure, however, becomes increasingly more stable in oligomers, where hydrogen bonds can form between neighboring monomers. We explore the structure and stability of both prefibrillar oligomers that consist of mainly antiparallel β-sheets and fibrillar oligomers with only parallel β-sheets. Prefibrillar oligomers are polymorphic but typically take on a cylindrin-like shape composed of mostly antiparallel β-strands. At the concentration of the simulation, the aggregation free energy landscape is nearly downhill. We use umbrella sampling along a structural progress coordinate for interconversion between prefibrillar and fibrillar forms to identify a conversion pathway between these forms. The fibrillar oligomer only becomes favored over its prefibrillar counterpart in the pentamer where an interconversion bottleneck appears. The structural characterization of the pathway along with statistical mechanical perturbation theory allow us to evaluate the effects of concentration on the free energy landscape of aggregation as well as the effects of the Dutch and Arctic mutations associated with early onset of Alzheimer's disease.
關聯:	Proc. Natl. Acad. Sci. U.S.A., 113, 42, 11835
DOI:	10.1073/pnas.1612362113
顯示於類別:	[化學學系暨研究所] 期刊論文

文件中的檔案:

檔案	描述	大小	格式	瀏覽次數
Exploring the Aggregation Free Energy Landscape of the Amyloid-β Protein (1-40).pdf		1137Kb	Adobe PDF	1	檢視/開啟
index.html		0Kb	HTML	153	檢視/開啟

在機構典藏中所有的資料項目都受到原著作權保護.

TAIR相關文章

資料載入中.....