Zhu Lan, Chen Xiaoyu, Abola Enrique E, Jing Liang, Liu Wei
Biodesign Center for Applied Structural Discovery, Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA; School of Molecular Sciences, Arizona State University, Tempe, AZ 85287, USA.
Biodesign Center for Applied Structural Discovery, Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA; School of Molecular Sciences, Arizona State University, Tempe, AZ 85287, USA.
Trends Pharmacol Sci. 2020 Nov;41(11):830-839. doi: 10.1016/j.tips.2020.08.009. Epub 2020 Sep 16.
Rational drug discovery has greatly accelerated the development of safer and more efficacious therapeutics, assisted significantly by insights from experimentally determined 3D structures of ligands in complex with their targets. Serial crystallography (SX) with X-ray free-electron lasers has enabled structural determination using micrometer- or nanometer-size crystals. This technology, applied in the past decade to solve structures of notoriously difficult-to-study drug targets at room temperature, has now been adapted for use in synchrotron radiation facilities. Ultrashort time scales allow time-resolved characterization of dynamic structural changes and pave the road to study the molecular mechanisms by 'molecular movie.' This article summarizes the latest progress in SX technology and deliberates its demanding applications in future structure-based drug discovery.
合理的药物发现极大地加速了更安全、更有效的治疗药物的开发，实验测定的配体与其靶点复合物的三维结构所提供的见解对此起到了显著的辅助作用。利用X射线自由电子激光的串行晶体学（SX）能够使用微米或纳米尺寸的晶体进行结构测定。这项技术在过去十年中用于在室温下解析极难研究的药物靶点的结构，现在已被应用于同步辐射设施。超短时间尺度允许对动态结构变化进行时间分辨表征，并为通过“分子电影”研究分子机制铺平了道路。本文总结了SX技术的最新进展，并探讨了其在未来基于结构的药物发现中的苛刻应用。
