Zheyi Liu

Dr. Liu earned his Ph.D. in Analytical Chemistry from the University of Chinese Academy of Sciences from September 2011 to July 2017. Since July 2021, he has been an Associate Research Fellow at the Dalian Institute of Chemical Physics (DICP), Chinese Academy of Sciences (CAS). Focusing on the technological bottlenecks of top-down mass spectrometry (TDMS) for protein characterization, Dr. Liu has systematically carried out collaborative innovations in “instrument development – method innovation – drug-target elucidation,” centered on the novel principle of extreme ultraviolet (EUV) photodissociation. Leveraging the Dalian Coherent Light Source (DCLS), he developed the first wavelength-tunable EUV laser dissociation mass spectrometer, breaking through the efficiency limits of top-down dissociation and achieving >90% sequence coverage for protein variants. On this basis, he established the nTDMS-UVPD analytical method, successfully overcoming the “ensemble averaging effect” inherent in conventional solution-phase characterization, and enabling simultaneous single-residue-precision characterization of “sequence–modification–structure” with variant- and conformation-selectivity. Finally, he applied this innovative mass spectrometry technology to biomedical frontiers, precisely revealing the dynamic interactions and allosteric mechanisms of important drug–protein complexes. This fundamental innovation in “instrument–method–application” has successfully propelled mass spectrometry from one-dimensional sequencing to multidimensional “structure–function” comprehensive characterization, providing transformative technical support for breaking through the development bottlenecks of “undruggable” targets and deciphering the dynamic mechanisms of biological macromolecules.

Selected publications:
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