Nygaard Mads, Kragelund Birthe B, Papaleo Elena, Lindorff-Larsen Kresten
Structural Biology and NMR Laboratory, The Linderstrøm-Lang Centre for Protein Science, Department of Biology, University of Copenhagen, Copenhagen, Denmark; Computational Biology Laboratory, Danish Cancer Society Society Research Center, Copenhagen, Denmark.
Structural Biology and NMR Laboratory, The Linderstrøm-Lang Centre for Protein Science, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
Biophys J. 2017 Aug 8;113(3):550-557. doi: 10.1016/j.bpj.2017.06.042.
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.
内在无序蛋白质在整个生物学过程中发挥着重要作用，然而我们对其序列、结构特性和功能之间关系的理解仍不完整。然而，这些蛋白质的动态性质使其在结构表征方面存在困难。许多无序蛋白质可以呈现紧密和伸展两种构象，伸展程度可能受到调控且对功能很重要。在实验中，压缩程度和形状通常通过小角X射线散射实验或脉冲场梯度核磁共振扩散测量来确定，这两种方法分别提供了回转半径和流体力学半径的系综平均估计值。通常，这些实验会通过分子模拟来解释或用于验证模拟结果。据我们所知，我们在此提供了一种新的有效方法，可根据无序蛋白质链结构系综模型计算其流体力学半径。具体而言，从高分子物理学的基本概念出发，我们推导出了结构的回转半径与其流体力学比率之间的关系，该关系反过来可用于，例如，将模拟的构象系综与核磁共振扩散测量结果进行比较。当使用核磁共振扩散测量来约束分子模拟时，这种关系可能也很有价值。
