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arXiv 0905.0383q-bio.BM
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聚合物模型在分析蛋白质的福斯特共振能量转移实验中的准确性如何？

How accurate are polymer models in the analysis of Forster resonance energy transfer experiments on proteins?

E. P. O'Brien, G. Morrison, B. R. Brooks, D. Thirumalai

备注：
31 pages, 9 figures
发表信息：
J. Chem. Phys. (2009) 124903
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摘要：

单分子福斯特共振能量转移（FRET）实验被用来推断蛋白质的变性态系综（DSE）的性质。根据测量的平均FRET效率<E>，通过假设DSE可以被描述为聚合物来推断距离分布P（R）。P（R）的适当聚合物模型（高斯链、蠕虫状链或自回避行走）中的单个参数通过使计算值和测量值相等来确定<E>。为了评估这个“标准程序”的准确性，我们考虑广义劳斯模型（GRM），其属性[<E>和P（R）]可以解析计算，和蛋白质L的分子转移模型，准确的模拟可以作为盐酸胍（GdmCl）浓度的函数进行。使用<E>GRM和蛋白质L的精确计算，我们使用标准程序推断P（R）。我们发现，平均端到端的距离可以准确地推断（小于10%的相对误差）使用<E>和聚合物模型的P（R）。然而，提取的回转半径（Rg）和持续长度（lp）的值不太准确。在推断的R-g和LP的相对误差，相对于精确值，可以是高达25%，在最高的GdmCl浓度。我们提出了一个自我一致性测试，需要<E>通过连接染料在蛋白质中的不同残基的测量，以评估使用高斯模型描述DSE的有效性。应用自洽检验的GRM表明，即使对于这个简单的模型，高斯P（R）是不够的。对冷休克蛋白FRET效率的实验数据分析表明，DSE P（R）与高斯模型存在显著偏差。

英文摘要：

Single molecule Forster resonance energy transfer (FRET) experiments are used to infer the properties of the denatured state ensemble (DSE) of proteins. From the measured average FRET efficiency, <E>, the distance distribution P(R) is inferred by assuming that the DSE can be described as a polymer. The single parameter in the appropriate polymer model (Gaussian chain, Wormlike chain, or Self-avoiding walk) for P(R) is determined by equating the calculated and measured <E>. In order to assess the accuracy of this "standard procedure," we consider the generalized Rouse model (GRM), whose properties [<E> and P(R)] can be analytically computed, and the Molecular Transfer Model for protein L for which accurate simulations can be carried out as a function of guanadinium hydrochloride (GdmCl) concentration. Using the precisely computed <E> for the GRM and protein L, we infer P(R) using the standard procedure. We find that the mean end-to-end distance can be accurately inferred (less than 10% relative error) using <E> and polymer models for P(R). However, the value extracted for the radius of gyration (Rg) and the persistence length (lp) are less accurate. The relative error in the inferred R-g and lp, with respect to the exact values, can be as large as 25% at the highest GdmCl concentration. We propose a self-consistency test, requiring measurements of <E> by attaching dyes to different residues in the protein, to assess the validity of describing DSE using the Gaussian model. Application of the self-consistency test to the GRM shows that even for this simple model the Gaussian P(R) is inadequate. Analysis of experimental data of FRET efficiencies for the cold shock protein shows that at there are significant deviations in the DSE P(R) from the Gaussian model.

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