Inferring properties of disordered chains from FRET transfer efficiencies.
Inferring properties of disordered chains from FRET transfer efficiencies.
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DOI：
10.1063/1.5006954
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发表时间：
2018-02
期刊：
影响因子：
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通讯作者：
Wenwei Zheng;Gül H. Zerze;A. Borgia;J. Mittal;B. Schuler;R. Best
中科院分区：
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作者：
Wenwei Zheng;Gül H. Zerze;A. Borgia;J. Mittal;B. Schuler;R. Best
Förster共振能量转移(FRET)是阐明未折叠或无序生物分子的结构和动力学性质的有力工具，特别是在单分子实验中。然而，关键的观察量，即供体和受体发色团的平均转移效率和荧光寿命，是在供体-受体距离的广泛分布上平均的。因此，所推断的系综的平均性质取决于被选择来描述距离的模型分布的形式，这已经被广泛地认识到。此外，虽然一种类型的聚合物模型的分布可能适合于在给定的一组物理化学条件下的链，但它可能不适合于不同环境中的同一链，因此即使在所有条件下表面上一致地应用相同的模型，也可能扭曲链尺寸随温度或溶液组成的变化而发生的明显变化。在这里，我们提出了一种从FRET数据确定系综性质的替代和直接的方法，其中允许聚合物标度指数随溶液条件变化。在其最简单的形式中，它需要平均FRET效率或荧光寿命信息。为了测试该方法的准确性，我们使用了30个不同蛋白质序列的隐式和显式溶剂模拟的合成FRET数据，以及内在无序和变性蛋白质的实验单分子FRET数据。在所有情况下，我们发现推断的回转半径都在真实值的10%以内，因此提供了比更简单的聚合物模型更高的精度。此外，由我们的程序得到的标度指数与由分子系综直接确定的标度指数符合得很好。我们的方法原则上可以推广到处理来自实验数据的其他分子内距离的系综平均函数。
Förster resonance energy transfer (FRET) is a powerful tool for elucidating both structural and dynamic properties of unfolded or disordered biomolecules, especially in single-molecule experiments. However, the key observables, namely, the mean transfer efficiency and fluorescence lifetimes of the donor and acceptor chromophores, are averaged over a broad distribution of donor-acceptor distances. The inferred average properties of the ensemble therefore depend on the form of the model distribution chosen to describe the distance, as has been widely recognized. In addition, while the distribution for one type of polymer model may be appropriate for a chain under a given set of physico-chemical conditions, it may not be suitable for the same chain in a different environment so that even an apparently consistent application of the same model over all conditions may distort the apparent changes in chain dimensions with variation of temperature or solution composition. Here, we present an alternative and straightforward approach to determining ensemble properties from FRET data, in which the polymer scaling exponent is allowed to vary with solution conditions. In its simplest form, it requires either the mean FRET efficiency or fluorescence lifetime information. In order to test the accuracy of the method, we have utilized both synthetic FRET data from implicit and explicit solvent simulations for 30 different protein sequences, and experimental single-molecule FRET data for an intrinsically disordered and a denatured protein. In all cases, we find that the inferred radii of gyration are within 10% of the true values, thus providing higher accuracy than simpler polymer models. In addition, the scaling exponents obtained by our procedure are in good agreement with those determined directly from the molecular ensemble. Our approach can in principle be generalized to treating other ensemble-averaged functions of intramolecular distances from experimental data.