Characterizing the first steps of amyloid formation for the ccbeta peptide.
Characterizing the first steps of amyloid formation for the ccbeta peptide.
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表征 ccbeta 肽淀粉样蛋白形成的第一步。
DOI：
10.1021/jp801222x
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Strodel B
中科院分区：
文献类型：
--
作者：
Strodel B
我们采用恒温和复制交换分子动力学，使用统一原子势和隐式溶剂表示来调查ccβ肽的自由能景观。从实验线圈结构出发，观察到温度升高时α向β的转变，与实验结果一致。各种β-薄片三聚体被确定为自由能最小值，包括一个与先前从实验数据中提出的淀粉样β-薄片模型非常相似的三聚体。我们描述了通往β-薄片的两种可选途径。第一种途径是通过直接的α到β转化而不发生三聚体的解离，第二种途径可以归类为解离/再结合途径。
We employ constant-temperature and replica exchange molecular dynamics to survey the free energy landscape of the ccβ peptide using a united-atom potential and an implicit solvent representation. Starting from the experimental coiled-coil structure we observe α to β conversion on increasing the temperature, in agreement with experiment. Various β-sheet trimers are identified as free energy minima, including one that closely resembles the amyloid β-sheet model previously proposed from experimental data. We characterize two alternative pathways leading to β-sheets. The first proceeds via direct α to β conversion without dissociation of the trimer, and the second can be classified as a dissociation/reassociation pathway.