Amplitudes and directions of internal protein motions from a JAM analysis of 15N relaxation data
Amplitudes and directions of internal protein motions from a JAM analysis of 15N relaxation data
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DOI：
10.1002/mrc.1839
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发表时间：
2006-07-01
影响因子：
2
通讯作者：
Wagner, Gerhard
中科院分区：
文献类型：
--
作者：
Kitao, Akio;Wagner, Gerhard
提出了一种利用核磁共振约束和N-15弛豫数据表征溶液中蛋白质动态结构的方法。该方法基于最小值间跳跃模型的概念。在这个模型中，我们假设蛋白质动力学可以在构象亚态的基础上描述，并涉及亚态内和亚态间的运动。通过从符合几何核磁共振约束的构象空间中选取能量最小化的构象来产生一组基态。在类似于10 ps的时间尺度上发生的亚态内运动，用分子动力学（MD）计算与力场能量项进行了模拟。确定构象基态的统计权重以再现核磁共振弛豫参数。精化过程包括四个阶段：G)确定满足核磁共振约束的结构集合，（ii）确定亚态内波动，（iii）确定构象亚态的统计权重以重现无模型松弛参数，以及对所得动态结构进行氧化石墨烯分析以确定蛋白质内部运动的幅度和方向。采用该方法研究了人CD2 （hCD2）在溶液中的粘附结构域的结构和动力学。通过改进确定了两个主要的集体模态，它们对原子均方波动的贡献总计为77.1%。第一种模式被解释为由一部分B-C环、一部分F链和F- g环组成的蛋白质片段的刚体运动。另一种类型的较小的振幅模式是为C'-C"回路。这些运动主要影响微凹的反受体结合部位的曲率，并表示凹（闭合）与平（开放）结合面之间的转换。通过对比溶液中的整体结构和具有反受体CD58的复杂结构，我们发现这两种运动类似于反受体结合后的变化。版权所有(C) 2006 John Wiley & Sons, Ltd。
A method has been developed for characterizing dynamic structures of proteins in solution by using nuclear magnetic resonance (NMR) restraints and N-15 relaxation data. This method is based on the concept of the jumping-among-minima (JAM) model. In this model we assume that protein dynamics can be described on the basis of conformational substates, and involves intra- and inter-substate motion. A set of substates is created by picking energy-minimized conformations from the conformational space consistent with the geometric NMR restraints. Intra-substate motions, which occur on the timescale of similar to 10 ps, are simulated with molecular dynamics (MD) calculations with force-field energy terms. Statistical weights of the conformational substates are determined to reproduce the NMR relaxation parameters. The refinement procedure consists of four stages: G) determination of the ensemble of structures that satisfy NMR restraints, (ii) determination of intra-substate fluctuation, (iii) determination of statistical weights of conformational substates to reproduce model-free relaxation parameters, and GO analysis of the resulting dynamic structure to determine amplitudes and directions of internal protein motions. This method was employed to investigate structure and dynamics of the adhesion domain of human CD2 (hCD2) in solution. Two major collective modes, whose contributions to atomic mean-square fluctuations are 77.1% in total, are identified by the refinement. The first mode is interpreted as a rigid-body motion of a protein segment consisting of a part of the B-C loop, a part of the F strand, and the F-G loop. Another type of smaller-amplitude mode is indicated for the C'-C" loop. The motions affect primarily the curvature of the slightly concave counterreceptor-binding site and represent transitions between a concave (closed) and flat (open) binding face. By comparing the ensemble of structures in solution to the complex structure with counterreceptor CD58, we found that these two types of motions resemble the change upon counterreceptor binding. Copyright (C) 2006 John Wiley & Sons, Ltd.