Structural motifs in protein cores and at protein-protein interfaces are different
Structural motifs in protein cores and at protein-protein interfaces are different
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DOI：
10.1002/pro.3996
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发表时间：
2020-11-20
期刊：
影响因子：
8
通讯作者：
Vakser, Ilya A.
中科院分区：
文献类型：
--
作者：
Hadarovich, Anna;Chakravarty, Devlina;Vakser, Ilya A.
蛋白质和蛋白质-蛋白质复合物的结构由相同的物理原理决定，因此具有许多相似之处。与此同时，可能存在差异，因为为了发挥功能，蛋白质与其他分子相互作用，经历构象变化等，这可能对三级结构和四级结构施加不同的限制。本研究的重点是蛋白质-蛋白质界面的结构特性相比，蛋白质的核心，基于丰富的现有结构数据和新的结构为基础的方法。结果表明，蛋白质核心和蛋白质-蛋白质界面的氨基酸组成、残基-残基接触偏好、亲/疏水性分布等物理化学特征具有相似性。另一方面，反映进化压力的特征，如结构组成和包装，在很大程度上是不同的。这些结果为蛋白质结构和功能的基本性质提供了重要的见解。同时，这些结果有助于更好地理解对接蛋白质的方法。在预测单个蛋白质结构方面的最新进展是在深度学习技术和残基协同进化数据新方法的进步之后取得的。蛋白质核心可以为深度学习在对接中的应用提供大量数据。然而，我们的研究结果表明，核心基序是显着不同的蛋白质-蛋白质界面，因此可能不会直接用于对接。同时，这种差异可能有助于克服应用共进化数据进行对接的一个主要障碍--对与对接不直接相关的分子内信息的区分。
Structures of proteins and protein-protein complexes are determined by the same physical principles and thus share a number of similarities. At the same time, there could be differences because in order to function, proteins interact with other molecules, undergo conformations changes, and so forth, which might impose different restraints on the tertiary versus quaternary structures. This study focuses on structural properties of protein-protein interfaces in comparison with the protein core, based on the wealth of currently available structural data and new structure-based approaches. The results showed that physicochemical characteristics, such as amino acid composition, residue-residue contact preferences, and hydrophilicity/hydrophobicity distributions, are similar in protein core and protein-protein interfaces. On the other hand, characteristics that reflect the evolutionary pressure, such as structural composition and packing, are largely different. The results provide important insight into fundamental properties of protein structure and function. At the same time, the results contribute to better understanding of the ways to dock proteins. Recent progress in predicting structures of individual proteins follows the advancement of deep learning techniques and new approaches to residue coevolution data. Protein core could potentially provide large amounts of data for application of the deep learning to docking. However, our results showed that the core motifs are significantly different from those at protein-protein interfaces, and thus may not be directly useful for docking. At the same time, such difference may help to overcome a major obstacle in application of the coevolutionary data to docking-discrimination of the intramolecular information not directly relevant to docking.