StructureDistiller: Structural relevance scoring identifies the most informative entries of a contact map
StructureDistiller: Structural relevance scoring identifies the most informative entries of a contact map
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DOI：
10.1038/s41598-019-55047-4
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发表时间：
2019-12-06
影响因子：
4.6
通讯作者：
Labudde, Dirk
中科院分区：
文献类型：
--
作者：
Bittrich, Sebastian;Schroeder, Michael;Labudde, Dirk
蛋白质折叠和结构预测是同一枚硬币的两个方面。接触图和基于约束的结构重建的相关技术可以被认为是两个过程的统一方面。我们提出了结构相关性（SR）分数，它量化了整个原生结构背景下的个体接触和残基的信息内容。蛋白质折叠的物理过程通常以空间和时间分辨率为特征：一些残基是早期折叠，而另一些残基对于展开事件高度稳定。我们采用所提出的 SR 分数来证明折叠起始和结构稳定是由不同残基组实现的子过程。细胞色素 c 的示例用于演示 StructureDistiller 如何识别正确蛋白质折叠所需的最重要的接触点。这表明接触图的条目与结构完整性的相关性并不相同。所提出的 StructureDistiller 算法可识别信息含量最高的联系人；这些条目传达了其他联系人未捕获的独特约束。识别信息最丰富的联系人，可以有效地使针对本地联系人地图中未观察到的联系人的恢复能力加倍。此外，这一知识将稀疏接触图的重建保真度显着提高了 0.4 埃。
Protein folding and structure prediction are two sides of the same coin. Contact maps and the related techniques of constraint-based structure reconstruction can be considered as unifying aspects of both processes. We present the Structural Relevance (SR) score which quantifies the information content of individual contacts and residues in the context of the whole native structure. The physical process of protein folding is commonly characterized with spatial and temporal resolution: some residues are Early Folding while others are Highly Stable with respect to unfolding events. We employ the proposed SR score to demonstrate that folding initiation and structure stabilization are subprocesses realized by distinct sets of residues. The example of cytochrome c is used to demonstrate how StructureDistiller identifies the most important contacts needed for correct protein folding. This shows that entries of a contact map are not equally relevant for structural integrity. The proposed StructureDistiller algorithm identifies contacts with the highest information content; these entries convey unique constraints not captured by other contacts. Identification of the most informative contacts effectively doubles resilience toward contacts which are not observed in the native contact map. Furthermore, this knowledge increases reconstruction fidelity on sparse contact maps significantly by 0.4 angstrom.