An Efficient Method for Estimating the Hydrodynamic Radius of Disordered Protein Conformations
An Efficient Method for Estimating the Hydrodynamic Radius of Disordered Protein Conformations
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DOI：
10.1016/j.bpj.2017.06.042
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发表时间：
2017-08-08
影响因子：
3.4
通讯作者：
Lindorff-Larsen, Kresten
中科院分区：
文献类型：
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作者：
Nygaard, Mads;Kragelund, Birthe B.;Lindorff-Larsen, Kresten
内部无序蛋白在整个生物学中发挥着重要作用，但我们对其序列，结构特性和功能之间关系的理解仍然不完整。然而，这些蛋白质的动态性质使得它们难以在结构上表征。许多无序的蛋白质可以达到紧凑和扩展的构象，和扩展的水平可以调节和重要的功能。在实验上，压实和形状的水平通常是由小角度X射线散射实验或脉冲场梯度NMR扩散测量，提供整体平均估计的回转半径和流体动力学半径，分别确定。通常，这些实验使用分子模拟来解释或用于验证它们。在这里，我们提供了一个新的和有效的方法来计算一个无序的蛋白质链的流体动力学半径从其结构系综模型。特别是，从聚合物物理学的基本概念出发，我们推导出结构的回转半径和其流体动力学比之间的关系，这反过来又可以用来，例如，比较模拟的构象合奏NMR扩散测量。当使用NMR扩散测量来抑制分子模拟时，该关系也可能是有价值的。
Intrinsically disordered proteins play important roles throughout biology, yet our understanding of the relationship between their sequences, structural properties, and functions remains incomplete. The dynamic nature of these proteins, however, makes them difficult to characterize structurally. Many disordered proteins can attain both compact and expanded conformations, and the level of expansion may be regulated and important for function. Experimentally, the level of compaction and shape is often determined either by small-angle x-ray scattering experiments or pulsed-field-gradient NMR diffusion measurements, which provide ensemble-averaged estimates of the radius of gyration and hydrodynamic radius, respectively. Often, these experiments are interpreted using molecular simulations or are used to validate them. We here provide, to our knowledge, a new and efficient method to calculate the hydrodynamic radius of a disordered protein chain from a model of its structural ensemble. In particular, starting from basic concepts in polymer physics, we derive a relationship between the radius of gyration of a structure and its hydrodynamic ratio, which in turn can be used, for example, to compare a simulated ensemble of conformations to NMR diffusion measurements. The relationship may also be valuable when using NMR diffusion measurements to restrain molecular simulations.