van den Bedem Henry, Fraser James S
1] Joint Center for Structural Genomics, Stanford Synchrotron Radiation Lightsource, Stanford University, Menlo Park, California, USA. [2] Division of Biosciences, SLAC National Accelerator Laboratory, Stanford University, Menlo Park, California, USA.
1] Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California, USA. [2] California Institute for Quantitative Biology, University of California, San Francisco, San Francisco, California, USA.
Nat Methods. 2015 Apr;12(4):307-18. doi: 10.1038/nmeth.3324.
Biomolecules adopt a dynamic ensemble of conformations, each with the potential to interact with binding partners or perform the chemical reactions required for a multitude of cellular functions. Recent advances in X-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy and other techniques are helping us realize the dream of seeing--in atomic detail--how different parts of biomolecules shift between functional substates using concerted motions. Integrative structural biology has advanced our understanding of the formation of large macromolecular complexes and how their components interact in assemblies by leveraging data from many low-resolution methods. Here, we review the growing opportunities for integrative, dynamic structural biology at the atomic scale, contending there is increasing synergistic potential between X-ray crystallography, NMR and computer simulations to reveal a structural basis for protein conformational dynamics at high resolution.
生物分子呈现出动态的构象集合，每种构象都有可能与结合伴侣相互作用或进行众多细胞功能所需的化学反应。X射线晶体学、核磁共振（NMR）光谱学和其他技术的最新进展正在帮助我们实现梦想，即从原子细节上了解生物分子的不同部分如何通过协同运动在功能亚状态之间转换。整合结构生物学通过利用来自许多低分辨率方法的数据，加深了我们对大型大分子复合物形成及其组件在组装中如何相互作用的理解。在这里，我们回顾了原子尺度上整合动态结构生物学不断增长的机会，认为X射线晶体学、NMR和计算机模拟之间的协同潜力越来越大，能够在高分辨率下揭示蛋白质构象动力学的结构基础。
