期刊論文
| 學年 | 106 |
|---|---|
| 學期 | 1 |
| 出版（發表）日期 | 2017-10-23 |
| 作品名稱 | Comparing the Aggregation Free Energy Landscapes of Amyloid Beta(1–42) and Amyloid Beta(1–40) |
| 作品名稱（其他語言） | |
| 著者 | Weihua Zheng; Min-Yeh Tsai; Peter G. Wolynes |
| 單位 | |
| 出版者 | |
| 著錄名稱、卷期、頁數 | Journal of the American Chemical Society 139 (46), pp 16666–16676 |
| 摘要 | Using a predictive coarse-grained protein force field, we compute and compare the free energy landscapes and relative stabilities of amyloid-β protein (1–42) and amyloid-β protein (1–40) in their monomeric and oligomeric forms up to the octamer. At the same concentration, the aggregation free energy profile of Aβ42 is more downhill, with a computed solubility that is about 10 times smaller than that of Aβ40. At a concentration of 40 μM, the clear free energy barrier between the pre-fibrillar tetramer form and the fibrillar pentamer in the Aβ40 aggregation landscape disappears for Aβ42, suggesting that the Aβ42 tetramer has a more diverse structural range. To further compare the landscapes, we develop a cluster analysis based on the structural similarity between configurations and use it to construct an oligomerization map that captures the paths of easy interconversion between different but structurally similar states of oligomers for both species. A taxonomy of the oligomer species based on β-sheet stacking topologies is proposed. The comparison of the two oligomerization maps highlights several key differences in the landscapes that can be attributed to the two additional C-terminal residues that Aβ40 lacks. In general, the two terminal residues strongly stabilize the oligomeric structures for Aβ42 relative to Aβ40, and greatly facilitate the conversion from pre-fibrillar trimers to fibrillar tetramers. |
| 關鍵字 | |
| 語言 | en_US |
| ISSN | |
| 期刊性質 | 國外 |
| 收錄於 | SCI |
| 產學合作 | |
| 通訊作者 | Peter G. Wolynes |
| 審稿制度 | 是 |
| 國別 | USA |
| 公開徵稿 | |
| 出版型式 | ,電子版,紙本 |
| 相關連結 |
機構典藏連結 ( http://tkuir.lib.tku.edu.tw:8080/dspace/handle/987654321/115400 ) |