Evaluating Models of Varying Complexity of Crowded Intrinsically Disordered Protein Solutions Against SAXS
Evaluating Models of Varying Complexity of Crowded Intrinsically Disordered Protein Solutions Against SAXS
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DOI：
10.1021/acs.jctc.9b00723
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发表时间：
2019-12-01
影响因子：
5.5
通讯作者：
Skepo, Marie
中科院分区：
文献类型：
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作者：
Fagerberg, Eric;Lenton, Samuel;Skepo, Marie
内源性无序蛋白在溶液中具有异质性构象。构象系综的性质取决于溶液条件，包括离子的存在、温度和拥挤，并且通常直接影响生物功能。许多体外研究集中在稀释条件下，而不是拥挤的环境中发现的体内流离失所者的属性。由于他们的异质性，在拥挤的条件下，国内流离失所者的研究是具有挑战性的实验和计算。尽管如此，由于对生物学相关现象的深入了解，这些研究是值得进行的。在这里，我们研究了在低盐和高盐条件下自拥挤条件下的高度带电的IDP组胺素5。小角度X射线散射和不同的模拟模型的组合，跨越一系列的计算复杂性和细节，使用。与实验结果相比，大多数模型的应用范围有限。性能最好的模型是高度粗粒度的珠子项链模型。该模型表明，组胺素5具有保守的回转半径和随着蛋白质浓度的增加而降低的灵活性。由于其计算效率，我们建议，它是一个合适的模型来研究拥挤的IDP解决方案，尽管它的简单。
Intrinsically disordered proteins (IDPs) adopt heterogeneous conformational ensembles in solution. The properties of the conformational ensemble are dependent upon the solution conditions, including the presence of ions, temperature, and crowding, and often directly impact biological function. Many in vitro investigations focus on the properties of IDPs under dilute conditions, rather than the crowded environment found in vivo. Due to their heterogeneous nature, the study of IDPs under crowded conditions is challenging both experimentally and computationally. Despite this, such studies are worth pursuing due to the insight gained into biologically relevant phenomena. Here, we study the highly charged IDP Histatin 5 under self-crowded conditions in low and high salt conditions. A combination of small-angle X-ray scattering and different simulation models, spanning a range of computational complexity and detail, is used. Most models are found to have limited application when compared to results from experiments. The best performing model is the highly coarse-grained, bead-necklace model. This model shows that Histatin 5 has a conserved radius of gyration and a decreasing flexibility with increasing protein concentration. Due to its computational efficiency, we propose that it is a suitable model to study crowded IDP solutions, despite its simplicity.