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Curr Protein Pept Sci. 2012 Feb;13(1):55-75. doi: 10.2174/138920312799277901.
While the crucial role of intrinsically disordered proteins (IDPs) in the cell cycle is now recognized, deciphering their molecular mode of action at the structural level still remains highly challenging and requires a combination of many biophysical approaches. Among them, small angle X-ray scattering (SAXS) has been extremely successful in the last decade and has become an indispensable technique for addressing many of the fundamental questions regarding the activities of IDPs. After introducing some experimental issues specific to IDPs and in relation to the latest technical developments, this article presents the interest of the theory of polymer physics to evaluate the flexibility of fully disordered proteins. The different strategies to obtain 3-dimensional models of IDPs, free in solution and associated in a complex, are then reviewed. Indeed, recent computational advances have made it possible to readily extract maximum information from the scattering curve with a special emphasis on highly flexible systems, such as multidomain proteins and IDPs. Furthermore, integrated computational approaches now enable the generation of ensembles of conformers to translate the unique flexible characteristics of IDPs by taking into consideration the constraints of more and more various complementary experiment. In particular, a combination of SAXS with high-resolution techniques, such as x-ray crystallography and NMR, allows us to provide reliable models and to gain unique structural insights about the protein over multiple structural scales. The latest neutron scattering experiments also promise new advances in the study of the conformational changes of macromolecules involving more complex systems.
虽然无序蛋白（IDP）在细胞周期中的关键作用现在已经得到认可，但在结构水平上破译它们的分子作用模式仍然极具挑战性，需要结合许多生物物理方法。其中，小角 X 射线散射（SAXS）在过去十年中取得了巨大成功，已成为解决许多关于 IDP 活性的基本问题不可或缺的技术。本文在介绍与 IDP 相关的一些特定实验问题以及最新技术发展之后，介绍了高分子物理理论在评估完全无序蛋白的柔韧性方面的意义。然后，回顾了获得溶液中自由和复合物中结合的 IDP 的三维模型的不同策略。实际上，最近的计算进展使得可以从散射曲线中轻松提取最大信息，特别强调了高度灵活的系统，例如多结构域蛋白和 IDP。此外，综合计算方法现在能够生成构象集合，通过考虑越来越多的各种互补实验的约束，来转化 IDP 的独特灵活特性。特别是 SAXS 与高分辨率技术（如 X 射线晶体学和 NMR）的结合，使我们能够提供可靠的模型，并在多个结构尺度上获得关于蛋白质的独特结构见解。最新的中子散射实验也有望在涉及更复杂系统的大分子构象变化研究方面取得新的进展。
