An Extended Guinier Analysis for Intrinsically Disordered Proteins.
An Extended Guinier Analysis for Intrinsically Disordered Proteins.
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DOI：
10.1016/j.jmb.2018.03.007
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发表时间：
2018-08-03
影响因子：
5.6
通讯作者：
Best RB
中科院分区：
文献类型：
--
作者：
Zheng W;Best RB
Guinier分析允许在非常小的散射角的限制下，从X射线或中子散射数据中无模型地确定生物分子的旋转半径(Rg)。对于球状蛋白，它的有效性范围是众所周知的，但对于未折叠或内在无序的蛋白(IDPs)，它的有效性受到更多限制。我们使用分子动力学模拟中的无序结构系综来研究在小散射角下哪些结构性质导致偏离Guinier近似。我们发现，与Guinier近似的偏差与描述未折叠系综的聚合物标度指数ν有关。因此，我们引入了经验的、依赖于ν的高阶校正项，以增强标准的Guinier分析。我们使用几个IDPs的全原子模拟数据以及一个IDP和一个折叠蛋白质的不稳定突变体的实验数据来测试新的拟合方案。在所有测试的情况下，我们实现了推断的RG的精度在真实RG的3%的∼内。该方法易于实现，并将有效范围扩展到最大QRG为∼2，而吉尼尔分析的∼为1.1。与Guinier或Debai方法相比，我们的方法允许从更宽的角度和更低的噪声使用数据来准确地分析散射数据。除了Rg，我们的拟合方案还给出了标度指数ν的估计，与从基本分子系综确定的参考ν非常一致。
Guinier analysis allows model-free determination of the radius of gyration (Rg) of a biomolecule from X-ray or neutron scattering data, in the limit of very small scattering angles. Its range of validity is well understood for globular proteins, but is known to be more restricted for unfolded or intrinsically disordered proteins (IDPs). We have used ensembles of disordered structures from molecular dynamics simulations to investigate which structural properties cause deviations from the Guinier approximation at small scattering angles. We find that the deviation from the Guinier approximation is correlated with the polymer scaling exponent ν describing the unfolded ensemble. We therefore introduce an empirical, ν-dependent, higher-order correction term, to augment the standard Guinier analysis. We test the new fitting scheme using all-atom simulation data for several IDPs and experimental data for both an IDP and a destabilized mutant of a folded protein. In all cases tested, we achieve an accuracy of the inferred Rg within ∼3% of the true Rg. The method is straightforward to implement and extends the range of validity to a maximum qRg of ∼ 2, versus ∼ 1.1 for Guinier analysis. Compared with the Guinier or Debye approaches, our method allows data from wider angles with lower noise to be used to analyze scattering data accurately. In addition to Rg, our fitting scheme also yields estimates of the scaling exponent ν in excellent agreement with the reference ν determined from the underlying molecular ensemble.
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影响因子：
16.6
作者：
通讯作者：
--
影响因子：
64.8
作者：
Demarest, SJ;Martinez-Yamout, M;Wright, PE
通讯作者：
Wright, PE
DOI：
10.1021/j150451a002
发表时间：
1947-01-01
期刊：
JOURNAL OF PHYSICAL AND COLLOID CHEMISTRY
影响因子：
--
作者：
DEBYE, P
通讯作者：
DEBYE, P
影响因子：
3.8
作者：
CALMETTES, P;DURAND, D;SMITH, JC
通讯作者：
SMITH, JC
影响因子：
2.9
作者：
Dunker, AK;Lawson, JD;Obradovic, Z
通讯作者：
Obradovic, Z