Insights into protein flexibility: The relationship between normal modes and conformational change upon protein-protein docking
Insights into protein flexibility: The relationship between normal modes and conformational change upon protein-protein docking
复制标题
DOI：
10.1073/pnas.0802496105
复制
发表时间：
2008-07-29
影响因子：
11.1
通讯作者：
Sternberg, Michael J. E.
中科院分区：
文献类型：
--
作者：
Dobbins, Sara E.;Lesk, Victor I.;Sternberg, Michael J. E.
了解蛋白质相互作用对于识别机制、蛋白质设计以及为未表征的蛋白质分配推定功能具有广泛的意义。研究蛋白质灵活性是描述蛋白质相互作用的挑战的关键组成部分。在这项工作中，我们描述了观察到的一组 20 种蛋白质的构象变化，这些蛋白质在关联时经历了大的构象变化（> 2 埃 C α RMSD），并询问系统的正常模式成功再现了哪些运动特征。我们证明，正常模式可用于识别移动区域，并在某些蛋白质中重现构象变化的方向。在 35% 的研究蛋白质中，发现单一低频正态模式可以很好地描述观察到的构象变化的方向。最后，我们发现，对于来自对接基准的一组 134 种蛋白质，正常模式的特征频率可用于可靠地预测观察到的构象变化的程度。我们讨论了结果对蛋白质识别机制的影响。
Understanding protein interactions has broad implications for the mechanism of recognition, protein design, and assigning putative functions to uncharacterized proteins. Studying protein flexibility is a key component in the challenge of describing protein interactions. In this work, we characterize the observed conformational change for a set of 20 proteins that undergo large conformational change upon association (> 2 angstrom C alpha RMSD) and ask what features of the motion are successfully reproduced by the normal modes of the system. We demonstrate that normal modes can be used to identify mobile regions and, in some proteins, to reproduce the direction of conformational change. In 35% of the proteins studied, a single low-frequency normal mode was found that describes well the direction of the observed conformational change. Finally, we find that for a set of 134 proteins from a docking benchmark that the characteristic frequencies of normal modes can be used to predict reliably the extent of observed conformational change. We discuss the implications of the results for the mechanics of protein recognition.