蛋白药物高级结构的表征方法研究

doi:10.19803/j.1672-8629.20250615

摘要/Abstract

摘要： 目的系统分析及总结近年来用于解析蛋白药物高级结构的新方法,以应对其质量控制中面临的挑战,并为相关药物的结构解析提供参考。方法通过检索国内外相关文献,系统归纳了质谱法、冷冻电镜技术及人工智能预测在蛋白药物高级结构表征中的原理、应用特点与性能局限。结果不同表征技术在分辨率、高通量和动态信息捕获方面各具优势：质谱技术擅长解析构象动态,冷冻电镜可提供近原子级静态结构,而多技术融合与计算建模显著提升了复杂蛋白体系结构信息的完整性与可靠性。结论蛋白药物结构研究虽取得阶段性进步,但现有分析方法仍存在一些问题,需深入研究、开发新方法来实现更精准解析结构,为生物药研发与质量控制提供技术支撑。

关键词: 蛋白药物, 高级结构, 冷冻电镜, 氢氘交换质谱, AlphaFold

Abstract: Objective To summarize the recent advancements in methods used to characterize the higher-order structures of protein drugs in order to address the challenges to quality control and to provide references for structural analysis of related drugs. Methods By reviewing related literature, the principles and applications of and limitations to mass spectrometry, cryo-electron microscopy, and artificial intelligence prediction in the characterization of protein drug higher-order structures were synthesized. Results There were distinct advantages to different characterization techniques in terms of resolution, throughput, and dynamic information capture. Mass spectrometry excelled in analyzing conformational dynamics, cryo-electron microscopy provided near-atomic-level static structures, while the integration of multiple techniques and computational modeling significantly improved the integrity and reliability of structural information about complex protein systems. Conclusion Despite the progress that has been made in protein drug structure research, currently-used analytical methods are far from perfect. More research and the development of new methods are required to achieve more precise structural analysis, which are expected to provide technical support for the development and quality control of biological drugs.

Key words: Protein Therapeutics, Higher-Order Structure, Cryo-Electron Microscopy, Hydrogen-Deuterium Exchange Mass Spectrometry, AlphaFold

中图分类号:

R954.5

孟贺欣, 王悦, 刘有平, 刘博. 蛋白药物高级结构的表征方法研究[J]. 中国药物警戒, 2025, 22(10): 1177-1182.

MENG Hexin, WANG Yue, LIU Youping, LIU Bo. Characterization of Higher-Order Structures in Protein Pharmaceuticals: a Study of Methods and Advances[J]. Chinese Journal of Pharmacovigilance, 2025, 22(10): 1177-1182.

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https://zgywjj.magtechjournal.com/CN/Y2025/V22/I10/1177

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