Characterization of the Conformational Equilibrium between the Two Major Substates of RNase A Using NMR Chemical Shifts
Characterization of the Conformational Equilibrium between the Two Major Substates of RNase A Using NMR Chemical Shifts
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DOI：
10.1021/ja210951z
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发表时间：
2012-03-07
影响因子：
15
通讯作者：
Vendruscolo, Michele
中科院分区：
文献类型：
--
作者：
Camilloni, Carlo;Robustelli, Paul;Vendruscolo, Michele
在认识到NMR化学位移可用于蛋白质结构测定之后，最近在用于将该策略扩展到越来越大和复杂的蛋白质和蛋白质复合物的方法中取得了快速进展。剩下的一个主要挑战是开发方法来利用包含在天然状态的蛋白质的构象波动的化学位移的信息。在这项工作中，我们表明，它是可能的，以确定一个合奏的构象代表的自由能表面的RNA酶A使用化学位移作为复制平均约束在分子动力学模拟。该表面的分析表明，化学位移可以用来表征该蛋白质的两个主要亚态之间的构象平衡。
Following the recognition that NMR chemical shifts can be used for protein structure determination, rapid advances have recently been made in methods for extending this strategy for proteins and protein complexes of increasing size and complexity. A remaining major challenge is to develop approaches to exploit the information contained in the chemical shifts about conformational fluctuations in native states of proteins. In this work we show that it is possible to determine an ensemble of conformations representing the free energy surface of RNase A using chemical shifts as replica-averaged restraints in molecular dynamics simulations. Analysis of this surface indicates that chemical shifts can be used to characterize the conformational equilibrium between the two major substates of this protein.