Application of the random coil index to studying protein flexibility
Application of the random coil index to studying protein flexibility
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DOI：
10.1007/s10858-007-9208-0
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发表时间：
2008-01-01
影响因子：
2.7
通讯作者：
Wishart, David S.
中科院分区：
文献类型：
--
作者：
Berjanskii, Mark V.;Wishart, David S.
蛋白质的柔韧性是许多蛋白质与配体结合事件和酶活性的核心。然而，蛋白质运动的实验测量通常是困难的、繁琐的和容易出错的。因此，人们对开发更简单、更快速的量化蛋白质灵活性的方法非常感兴趣。最近，我们描述了一种称为随机线圈指数（RCI）的方法，该方法似乎能够仅使用主链化学位移来定量估计蛋白质结构集合体的无模型顺序参数和灵活性。由于其潜在的实用性，我们对RCI方法进行了更详细的调查，试图确定其基本原理，其一般实用性，对化学位移误差的敏感性，对数据完整性的敏感性，对其他蛋白质的适用性，以及其一般优点和缺点。总的来说，我们发现RCI方法非常稳健，并且它代表了研究蛋白质灵活性的传统方法的有用补充。我们已经将这里报告的许多发现和改进实现到web服务器中，该服务器允许直接从主链H-1， C-13和N-15化学位移分配中轻松，自动预测无模型顺序参数，MD RMSF和NMR RMSD值。该服务器可在http://wishart.biology.ualberta.ca/rci上获得。
Protein flexibility lies at the heart of many protein-ligand binding events and enzymatic activities. However, the experimental measurement of protein motions is often difficult, tedious and error-prone. As a result, there is a considerable interest in developing simpler and faster ways of quantifying protein flexibility. Recently, we described a method, called Random Coil Index (RCI), which appears to be able to quantitatively estimate model-free order parameters and flexibility in protein structural ensembles using only backbone chemical shifts. Because of its potential utility, we have undertaken a more detailed investigation of the RCI method in an attempt to ascertain its underlying principles, its general utility, its sensitivity to chemical shift errors, its sensitivity to data completeness, its applicability to other proteins, and its general strengths and weaknesses. Overall, we find that the RCI method is very robust and that it represents a useful addition to traditional methods of studying protein flexibility. We have implemented many of the findings and refinements reported here into a web server that allows facile, automated predictions of model-free order parameters, MD RMSF and NMR RMSD values directly from backbone H-1, C-13 and N-15 chemical shift assignments. The server is available at http://wishart.biology.ualberta.ca/rci.