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Synchrotron radiation as a tool for macromolecular X-Ray Crystallography: A XXI century perspective
Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms ( IF 1.4 ) Pub Date : 2021-01-05 , DOI: 10.1016/j.nimb.2020.12.016
Marek Grabowski 1 , David R Cooper 1 , Dariusz Brzezinski 1, 2, 3 , Joanna M Macnar 4, 5 , Ivan G Shabalin 1 , Marcin Cymborowski 1 , Zbyszek Otwinowski 6 , Wladek Minor 1
Affiliation  

Intense X-rays available at powerful synchrotron beamlines provide macromolecular crystallographers with an incomparable tool for investigating biological phenomena on an atomic scale. The resulting insights into the mechanism’s underlying biological processes have played an essential role and shaped biomedical sciences during the last 30 years, considered the “golden age” of structural biology. In this review, we analyze selected aspects of the impact of synchrotron radiation on structural biology. Synchrotron beamlines have been used to determine over 70% of all macromolecular structures deposited into the Protein Data Bank (PDB). These structures were deposited by over 13,000 different research groups. Interestingly, despite the impressive advances in synchrotron technologies, the median resolution of macromolecular structures determined using synchrotrons has remained constant throughout the last 30 years, at about 2 Å. Similarly, the median times from the data collection to the deposition and release have not changed significantly. We describe challenges to reproducibility related to recording all relevant data and metadata during the synchrotron experiments, including diffraction images. Finally, we discuss some of the recent opinions suggesting a diminishing importance of X-ray crystallography due to impressive advances in Cryo-EM and theoretical modeling. We believe that synchrotrons of the future will increasingly evolve towards a life science center model, where X-ray crystallography, Cryo-EM, other experimental and computational resources, and knowledge are encompassed within a versatile research facility. The recent response of crystallographers to the COVID-19 pandemic suggests that X-ray crystallography conducted at synchrotron beamlines will continue to play an essential role in structural biology and drug discovery for years to come.



中文翻译:


同步辐射作为大分子 X 射线晶体学的工具:二十一世纪的视角



强大的同步加速器光束线提供的强 X 射线为大分子晶体学家提供了在原子尺度上研究生物现象的无与伦比的工具。由此产生的对该机制的潜在生物过程的见解在过去 30 年(被认为是结构生物学的“黄金时代”)中发挥了重要作用,并塑造了生物医学科学。在这篇综述中,我们分析了同步加速器辐射对结构生物学影响的选定方面。同步加速器光束线已用于确定蛋白质数据库 (PDB) 中超过 70% 的大分子结构。这些结构由 13,000 多个不同的研究小组保存。有趣的是,尽管同步加速器技术取得了令人印象深刻的进步,但使用同步加速器测定的大分子结构的中值分辨率在过去 30 年中一直保持恒定,约为 2 Å。同样,从数据收集到沉积和发布的中位时间也没有显着变化。我们描述了在同步加速器实验期间记录所有相关数据和元数据(包括衍射图像)相关的再现性挑战。最后,我们讨论了一些最近的观点,这些观点表明,由于冷冻电镜和理论建模的令人瞩目的进步,X 射线晶体学的重要性正在下降。我们相信,未来的同步加速器将日益向生命科学中心模型发展,其中 X 射线晶体学、冷冻电镜、其他实验和计算资源以及知识都包含在多功能研究设施中。 晶体学家最近对 COVID-19 大流行的反应表明,在同步加速器光束线上进行的 X 射线晶体学将在未来几年继续在结构生物学和药物发现中发挥重要作用。

更新日期:2021-01-05
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