刘哲益

刘博士于2011年9月至2017年7月在中国科学院大学分析化学专业攻读博士学位；2021年7月起在中国科学院大连化学物理研究所任副研究员。刘博士聚焦蛋白质Top-Down质谱表征技术瓶颈，以“极紫外解离”新原理为核心，系统开展了“硬件创制-方法创新-药靶解析”的协同创新。依托大连相干光源（Dalian Coherent Light Source, DCLS），研制了首套波长可调谐极紫外激光解离质谱，突破了Top-Down解离效率极限，实现蛋白质变体序列覆盖率>90%；在此基础上，建立了nTDMS-UVPD分析新方法，成功克服了常规溶液相表征的“系综平均效应”，实现了变体与构象选择性的“序列-修饰-结构”同步单残基精度表征；最终，将该创新质谱技术应用于生物医药前沿，精准揭示了重要药物-蛋白的动态互作与变构机制。这一“装置-方法-应用”的底层创新，成功推动了质谱技术从单一的一维测序向“结构-功能”多维综合表征的跨越，为突破“不可成药”靶标研发瓶颈及破解生命大分子动态机制提供了变革性的技术支撑。

代表作：
1. Lingqiang Zhou#; Zheyi Liu#; Yongjie Guo; Shiwen Liu; Heng Zhao; Shan Zhao; Chunlei Xiao; Shun Feng*; Xueming Yang; Fangjun Wang*; Ultraviolet Photodissociation Reveals the Molecular Mechanism of Crown Ether Microsolvation Effect on the Gas-Phase Native-like Protein Structure, J Am Chem Soc, 2023, 145(2): 1285-1291
2. Yu Bai#; Zheyi Liu#; Yuanqing Li#; Heng Zhao; Can Lai; Shan Zhao; Kaixian Chen; Cheng Luo*; Xueming Yang; Fangjun Wang*; Structural Mass Spectrometry Probes the Inhibitor-Induced Allosteric Activation of CDK12/CDK13-Cyclin K Dissociation, J Am Chem Soc, 2023, 145(21): 11477-11481
3. Zheyi Liu#; Shirui Yang#; Lingqiang Zhou#; Min He; Yu Bai; Shan Zhao; Fangjun Wang; Structural characterization of protein-material interfacial interactions using lysine reactivity profiling-mass spectrometry, Nat Protoc, 2023, 18: 2600-2623
4. Pan Luo#; Zheyi Liu#; Can Lai; Zhixiong Jin; Mengdie Wang; Heng Zhao; Yu Liu; Weiqing; Zhang; Xingan Wang; Chunlei Xiao; Xueming Yang; and Fangjun Wang*; Time-Resolved Ultraviolet Photodissociation Mass Spectrometry Probes the Mutation-Induced Alterations in Protein Stability and Unfolding Dynamics, J Am Chem Soc, 2024, 146(13): 8832-8838
5. Yuanzhi Xie#; Zheyi Liu#; Huiwen Qin; Heng Zhao; Weiqing Zhang; Chunlei Xiao; Xian Wang*; Xueming Yang; Fangjun Wang*; Ultraviolet Photodissociation Mass Spectrometry Captures the Acyl Chain Length-Dependent Conformation Dynamics of Acyl Carrier Protein, J Am Chem Soc, 2025, 147(20): 16760-16765