Unfolding the fold of cyclic cysteine-rich peptides.
Unfolding the fold of cyclic cysteine-rich peptides.
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展开富含半胱氨酸的环状肽的折叠。
DOI：
10.1110/ps.073142708
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Clementi,Cecilia
中科院分区：
文献类型：
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作者：
Shehu,Amarda;Kavraki,LydiaE;Clementi,Cecilia
我们提出了一种方法来广泛表征天然状态的环半胱氨酸-富肽系。该方法使用最小信息，即氨基酸序列和环化，作为表征天然状态的拓扑特征。该方法不假设半胱氨酸的特定二硫键配对，并允许未配对的半胱氨酸的可能性。通过分层次的多分辨率勘探，获得了与原生状态相关的构象空间的详细视图。该勘探的一个关键特征是采用几何方法，有效地生成大量彼此独立的不同旋回构象。生成构象的空间和能量分析将自由能景观与探索的构象空间联系起来。对三种不同折叠方式的长环肽的分析表明，与自由能最小值相关的构象组合和半胱氨酸排列与现有实验数据完全一致。这些结果为环肽的天然状态特征提供了详细的分析，可以在实验中进一步测试。
We propose a method to extensively characterize the native state ensemble of cyclic cysteine‐rich peptides. The method uses minimal information, namely, amino acid sequence and cyclization, as a topological feature that characterizes the native state. The method does not assume a specific disulfide bond pairing for cysteines and allows the possibility of unpaired cysteines. A detailed view of the conformational space relevant for the native state is obtained through a hierarchic multi‐resolution exploration. A crucial feature of the exploration is a geometric approach that efficiently generates a large number of distinct cyclic conformations independently of one another. A spatial and energetic analysis of the generated conformations associates a free‐energy landscape to the explored conformational space. Application to three long cyclic peptides of different folds shows that the conformational ensembles and cysteine arrangements associated with free energy minima are fully consistent with available experimental data. The results provide a detailed analysis of the native state features of cyclic peptides that can be further tested in experiment.