Protein Motional Details Revealed by Complementary Structural Biology Techniques
Protein Motional Details Revealed by Complementary Structural Biology Techniques
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DOI：
10.1016/j.str.2020.06.001
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发表时间：
2020-09-01
期刊：
影响因子：
5.7
通讯作者：
Linser, Rasmus
中科院分区：
文献类型：
--
作者：
Grohe, Kristof;Patel, Snehal;Linser, Rasmus
蛋白质的功能依赖于确定的分子可塑性。如何全面正确地捕捉动态是普遍存在的生物学重要性。通常用于探测蛋白质动力学的方法包括通过NMR弛豫、基于分子动力学（MD）的方法和通过最近基于eNOE的多结构方法捕获动态系综内的子状态来无模型地阐明位点特异性运动。尽管MD有时与整体平均NMR约束相结合，但这些方法在很大程度上是单独开发和使用的。由于基本概念和实际要求不同，尚不清楚它们如何进行比较，以及它们如何相互验证和相互补充。在这里，我们提取和比较MD模拟，NMR弛豫测量，和eNOE为基础的多状态结构的鸡α-血影蛋白的SH 3域的差分信息内容。数据表明，一个有效的，一致的，详细的图片是可行的时间尺度和实际的构象状态采样的动态合奏。这包括生物学上重要的侧链可塑性，实验交叉验证的评估是一个重大的挑战。
Proteins depend on defined molecular plasticity for their functionality. How to comprehensively capture dynamics correctly is of ubiquitous biological importance. Approaches commonly used to probe protein dynamics include model-free elucidation of site-specific motion by NMR relaxation, molecular dynamics (MD)-based approaches, and capturing the substates within a dynamic ensemble by recent eNOE-based multiple-structure approaches. Even though MD is sometimes combined with ensemble-averaged NMR restraints, these approaches have largely been developed and used individually. Owing to the different underlying concepts and practical requirements, it has remained unclear how they compare, and how they cross-validate and complement each other. Here, we extract and compare the differential information contents of MD simulations, NMR relaxation measurements, and eNOE-based multi-state structures for the SH3 domain of chicken alpha-spectrin. The data show that a validated, consistent, and detailed picture is feasible both for timescales and actual conformational states sampled in the dynamic ensemble. This includes the biologically important side-chain plasticity, for which experimentally cross-validated assessment is a significant challenge.