Application of docking methodologies to modeled proteins
Application of docking methodologies to modeled proteins
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DOI：
10.1002/prot.25889
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发表时间：
2020-03-20
影响因子：
2.9
通讯作者：
Vakser, Ilya A.
中科院分区：
文献类型：
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作者：
Singh, Amar;Dauzhenka, Taras;Vakser, Ilya A.
蛋白质对接对蛋白质相互作用的结构表征至关重要。除了提供蛋白质复合物的结构外，蛋白质及其复合物的建模对于理解蛋白质相互作用的基本原理和特定方面也很重要。一般来说，蛋白质建模的准确性仍然低于实验方法。因此，研究对接技术对模型蛋白质的适用性是很重要的。我们提出了新的全面的蛋白质模型基准集，用于蛋白质对接的开发和验证，并在这些集上系统地评估了自由和基于模板的对接技术。与以往的研究不同，基准集反映了真实的案例建模/对接场景，模型的准确性由建模过程评估，而不参考本地结构（在实际应用中是未知的）。我们还扩展了分析，包括蛋白质对的对接，其中蛋白质具有不同的结构精度。结果表明，总体而言，基于模板的对接对模型结构误差的敏感性低于自由对接。基于模板的方法生成的近原生对接姿态通常也比自由对接产生的姿态具有更高的秩（尽管自由对接在拥挤的细胞环境中建模蛋白质相互作用的多样性是必不可少的）。结果表明，对接技术在较宽的建模精度范围内适用于蛋白质模型。该研究为对接到蛋白质模型的实际应用提供了明确的指导。
Protein docking is essential for structural characterization of protein interactions. Besides providing the structure of protein complexes, modeling of proteins and their complexes is important for understanding the fundamental principles and specific aspects of protein interactions. The accuracy of protein modeling, in general, is still less than that of the experimental approaches. Thus, it is important to investigate the applicability of docking techniques to modeled proteins. We present new comprehensive benchmark sets of protein models for the development and validation of protein docking, as well as a systematic assessment of free and template-based docking techniques on these sets. As opposed to previous studies, the benchmark sets reflect the real case modeling/docking scenario where the accuracy of the models is assessed by the modeling procedure, without reference to the native structure (which would be unknown in practical applications). We also expanded the analysis to include docking of protein pairs where proteins have different structural accuracy. The results show that, in general, the template-based docking is less sensitive to the structural inaccuracies of the models than the free docking. The near-native docking poses generated by the template-based approach, typically, also have higher ranks than those produces by the free docking (although the free docking is indispensable in modeling the multiplicity of protein interactions in a crowded cellular environment). The results show that docking techniques are applicable to protein models in a broad range of modeling accuracy. The study provides clear guidelines for practical applications of docking to protein models.