《生命科学》 2025, 37(7): 828-843

同步辐射小角散射技术在蛋白质科学研究中的应用与展望

李　娜^* , 刘广峰 , 李怡雯 , 宋攀奇 , 张建桥

中国科学院上海高等研究院国家蛋白质科学研究(上海)设施，上海 201210

摘　要：

同步辐射小角散射技术具有高通量、快速结构表征的特点，是溶液体系多尺度结构表征的研究利器，在蛋白质科学领域已得到广泛应用。位于上海同步辐射光源的BL19U2生物小角X射线散射线站(BioSAXS)，可以在1~100 纳米空间尺度以及毫秒时间尺度对生物大分子溶液活性结构进行表征。开放十年以来，BioSAXS 线站与国家蛋白质科学研究( 上海) 设施其他技术系统协同发展，围绕蛋白质领域关键科学问题，有针对性地进行原位实验装置与散射实验算法开发，显著提升了线站散射数据采集的效率和精度，为理解蛋白质在溶液中的动态结构及其功能机制提供了新的视角。本文介绍了全球BioSAXS 技术的发展现状以及技术演进。结合该技术在蛋白质科学研究中的典型应用案例，该文展望了BioSAXS 技术与人工智能以及其他结构生物学方法融合在蛋白质科学研究中的应用前景。

通讯作者：李　娜 , Email:lina02@sari.ac.cn

Synchrotron small-angle scattering in biological macromolecules: application and prospective

LI Na^* , LIU Guang-Feng , LI Yi-Wen , SONG Pan-Qi , ZHANG Jian-Qiao

National Facility for Protein Science in Shanghai, Shanghai Advanced Research Institute, Shanghai 201210, China

Abstract:

Synchrotron small-angle X-ray scattering is a powerful technique for high-throughput, rapid structural characterization of macromolecules in solution, which has become widely applied in structural characterization of biological macromolecules in solution. The BL19U2 biological small-angle X-ray scattering (BioSAXS) beamline at Shanghai Synchrotron Radiation Facility (SSRF) enables the structural characterization of biomolecules within wide spatial scales of 1–100 nanometers and temporal resolutions down to milliseconds. Since the year of 2015, BL19U2 has been integrated into the development of National Facility for Protein Science Shanghai (NFPS), providing integrative tools for elucidating the structures and dynamics of biomolecules. Over the past decade, BL19U2 has devoted to improve the performance of BioSAXS beamline, including the integration of automated sample changers, inline purification SEC-SAXS system, stop-flow/microfluidic devices for time-resolved measurements, and enrich sample environmental changer (eg. temperature, X-ray footprinting and pressure). These developments have substantially enhanced scattering data acquisition efficiency and data analysis precision, facilitating in situ investigations of protein conformational changes, protein/nucleic acid complex assembly processes, and evaluating structural stability under various conditions. In summary, this article reviews the global state and technique developments of BioSAXS, highlighting representative applications in the field of protein science. It also discusses the prospects of combining BioSAXS with artificiel intelligence (AI) to promote the scattering data processing and interpretation, enabling more understanding of structure-function relationships of biomolecules.

Communication Author：LI Na , Email:lina02@sari.ac.cn