Applications of contact predictions to structural biology.
Applications of contact predictions to structural biology.
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DOI：
10.1107/s2052252517005115
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发表时间：
2017-05-01
期刊：
影响因子：
3.9
通讯作者：
Rigden DJ
中科院分区：
文献类型：
--
作者：
Simkovic F;Ovchinnikov S;Baker D;Rigden DJ
最近的发展允许从多个蛋白质序列比对中提取准确的接触预测。这篇评论说明了多种方式，这些信息可能有助于实验结构生物学家。对蛋白质结构或功能很重要的分子内或分子间残基相互作用的进化压力可以导致两个位置之间的协方差。最近的方法进步允许更准确的接触预测来自这个进化协方差信号。接触预测的实际应用在很大程度上局限于结构生物信息学，然而，正如这项工作试图证明的那样，这些数据对从事X射线晶体衍射、冷冻EM或NMR工作的结构生物学家来说具有巨大的价值。像Rosetta这样的集成结构生物信息学软件包已经可以以各种方式利用接触预测。接触预测的贡献始于结构设计，其中结构域可能需要单独表示，接触预测可以帮助预测域限制。通过分子置换（MR）的结构解决方案以不同的方式受益于接触预测：在困难的情况下，当预测可用时，可以使用从头计算建模来构建更准确的搜索模型，而分子间接触预测可以允许构建更大的寡聚搜索模型。此外，使用超二级基序或针对PDB的大规模筛选的MR可以利用可以从接触预测推断的信息，例如靶标中任何β链配对的平行或反平行性质。通过帮助分配序列寄存器，接触信息在确定较低分辨率结构中将特别有价值。在大型复合物中，接触信息可以允许确定负责某个密度区域的蛋白质的身份，然后帮助在该密度内定位可用模型。在NMR中，预测的接触可以提供长程信息，以类似但补充实验方法的方式扩展该技术的尺寸上限。最后，预测的接触可以区分生物学相关的接口和纯粹的晶格接触在最终的晶体结构，并有可能在功能重要的区域的识别和突变的后果。
Recent developments allow the extraction of accurate contact predictions from multiple protein-sequence alignments. This review illustrates the manifold ways in which this information may assist the experimental structural biologist. Evolutionary pressure on residue interactions, intramolecular or intermolecular, that are important for protein structure or function can lead to covariance between the two positions. Recent methodological advances allow much more accurate contact predictions to be derived from this evolutionary covariance signal. The practical application of contact predictions has largely been confined to structural bioinformatics, yet, as this work seeks to demonstrate, the data can be of enormous value to the structural biologist working in X-ray crystallography, cryo-EM or NMR. Integrative structural bioinformatics packages such as Rosetta can already exploit contact predictions in a variety of ways. The contribution of contact predictions begins at construct design, where structural domains may need to be expressed separately and contact predictions can help to predict domain limits. Structure solution by molecular replacement (MR) benefits from contact predictions in diverse ways: in difficult cases, more accurate search models can be constructed using ab initio modelling when predictions are available, while intermolecular contact predictions can allow the construction of larger, oligomeric search models. Furthermore, MR using supersecondary motifs or large-scale screens against the PDB can exploit information, such as the parallel or antiparallel nature of any β-strand pairing in the target, that can be inferred from contact predictions. Contact information will be particularly valuable in the determination of lower resolution structures by helping to assign sequence register. In large complexes, contact information may allow the identity of a protein responsible for a certain region of density to be determined and then assist in the orientation of an available model within that density. In NMR, predicted contacts can provide long-range information to extend the upper size limit of the technique in a manner analogous but complementary to experimental methods. Finally, predicted contacts can distinguish between biologically relevant interfaces and mere lattice contacts in a final crystal structure, and have potential in the identification of functionally important regions and in foreseeing the consequences of mutations.