Main Research Interests
Drug discovery from original innovation is a major national need for implementing the Healthy China strategy. Our research focuses on discovering new inhibitors targeting novel sites of protein post-translational modifications. We have established a new NMR-based drug fragment screening model and developed methods to characterize low-abundance binding conformations. This led to breakthroughs in using NMR for lead drug discovery, facilitating the identification of several lead compounds, one of which has gained market recognition and entered preclinical studies. We unveiled the molecular mechanisms of target protein dynamic conformational changes and ligand recognition, leading to the reevaluation of seemingly undruggable targets. Additionally, we proposed a new fragment-based strategy for repurposing low-molecular-weight drugs against COVID-19, identifying several existing drugs targeting the main protease of the virus, providing crucial mechanistic support for ongoing clinical trials, such as those involving omeprazole.
Ph.D. Supervisor and Professor at the University of Science and Technology of China. Holds a bachelor's and master's degree from Peking University’s College of Chemistry and Molecular Engineering and a Ph.D. from Johns Hopkins University. Previously engaged in drug development at Pfizer USA and CRUK Beatson Institute in the UK.
Representative Papers from the Last Five Years
1. Gao J#, Liang E#, Ma R, Li F, Liu Y, Liu J, Jiang L, Li C, Dai H, Wu J, Su X, He W, Ruan K. Fluorine Pseudocontact Shifts Used for Characterizing the Protein-Ligand Interaction Mode in the Limit of NMR Intermediate Exchange. Angew. Chem. Int. Ed. 2017, 56:12982-12986.
2. Gao J#, Zhang L#, Liu X, Li F, Ma R, Zhu Z, Zhang J, Wu J, Shi Y, Pan Y, Ge Y, Ruan K. Repurposing Low-Molecular-Weight Drugs Against the Main Protease of Severe Acute Respiratory Syndrome Coronavirus 2. J. Phys. Chem. Lett. 2020, 11:7267–7272.
3. Lv M#, Gao J#, Li M#, Ma R, Li F, Liu Y, Liu M, Zhang J, Yao X, Wu J, Shi Y, Tang Y, Pan Y, Zhang Z, Ruan K. Conformational Selection in Ligand Recognition by the First Tudor Domain of PHF20L1. J. Phys. Chem. Lett. 2020, 11:7932-7938.
4. Xu D#, Li B#, Gao J#, Liu Z, Niu X, Nshogoza G, Zhang J, Wu J, Su XC, He W, Ma R, Yang D, Ruan K. Ligand Proton Pseudocontact Shifts Determined from Paramagnetic Relaxation Dispersion in the Limit of NMR Intermediate Exchange. J. Phys. Chem. Lett. 2018, 9:3361-3367.
5. Xu D, Ma R, Zhang J, Liu Z, Wu B, Peng J, Zhai Y, Gong Q, Shi Y, Wu J, Wu Q, Zhang Z, Ruan K. Dynamic Nature of CTCF Tandem 11 Zinc Fingers in Multivalent Recognition of DNA As Revealed by NMR Spectroscopy. J. Phys. Chem. Lett. 2018, 9:4020-4028.
Contact Information
E-mail: kruan@ustc.edu.cn