Protein dynamics from NMR: the slowly relaxing local structure analysis compared with model-free analysis.
Protein dynamics from NMR: the slowly relaxing local structure analysis compared with model-free analysis.
复制标题
NMR 的蛋白质动力学：缓慢松弛的局部结构分析与无模型分析的比较。
DOI：
10.1021/jp056975t
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Freed,JackH
中科院分区：
文献类型：
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作者：
Meirovitch,Eva;Shapiro,YuryE;Polimeno,Antonino;Freed,JackH
15 N-H自旋弛豫是一种获得蛋白质动力学信息的强大方法。传统的数据分析方法是无模型（MF），其中全局和局部N-H运动是独立的，并且局部几何结构被简化。常见的MF分析包括拟合单场数据。结果通常依赖于字段，并且多字段数据不能用标准拟合方案拟合。我们和其他人确定了MF未检测到已知功能动力学的情况。最近，我们适用于自旋弛豫蛋白质的缓慢放松的局部结构（SRLS）的方法，该帐户严格的模式混合和一般特征的局部几何。SRLS被证明在适当的渐近极限产生MF。我们发现实验谱密度与SRLS谱密度相当一致。MF公式经常在其有效范围之外使用，允许小数据集使用良好的统计数据进行强制拟合，但最佳拟合参数不准确。本文重点介绍了力配合的机理及其意义。结果表明，MF分析力拟合的实验数据，因为模式混合，菱形对称的局部有序和一般特征的局部几何形状不占。结合多场多温度数据分析的MF方法可能会导致不正确的现象的检测，和构象熵来自MF序参数可能是非常不准确的。另一方面，拟合到更合适的模型可以产生一致的物理上有洞察力的信息。这要求理论谱密度的复杂性与实验数据的完整性相匹配。如本文所示，SRLS谱密度符合此要求。
15N−H spin relaxation is a powerful method for deriving information on protein dynamics. The traditional method of data analysis is model-free (MF), where the global and local N−H motions are independent and the local geometry is simplified. The common MF analysis consists of fitting single-field data. The results are typically field-dependent, and multifield data cannot be fit with standard fitting schemes. Cases where known functional dynamics has not been detected by MF were identified by us and others. Recently we applied to spin relaxation in proteins the slowly relaxing local structure (SRLS) approach, which accounts rigorously for mode mixing and general features of local geometry. SRLS was shown to yield MF in appropriate asymptotic limits. We found that the experimental spectral density corresponds quite well to the SRLS spectral density. The MF formulas are often used outside of their validity ranges, allowing small data sets to be force-fitted with good statistics but inaccurate best-fit parameters. This paper focuses on the mechanism of force-fitting and its implications. It is shown that MF analysis force-fits the experimental data because mode mixing, the rhombic symmetry of the local ordering and general features of local geometry are not accounted for. Combined multifield multitemperature data analyzed with the MF approach may lead to the detection of incorrect phenomena, and conformational entropy derived from MF order parameters may be highly inaccurate. On the other hand, fitting to more appropriate models can yield consistent physically insightful information. This requires that the complexity of the theoretical spectral densities matches the integrity of the experimental data. As shown herein, the SRLS spectral densities comply with this requirement.