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Luhua Lai
Physical Chemistry，Biomolecular structure, function and design
Cheung Kong Professor
B.Sc., 1984, Peking University. M.Sc., 1987, Peking University. Ph.D., 1989, Peking University. 1998-1999, Berkeley Scholar, University of California at Berkeley.
Telephone: 010-62757486, 62757520; E-mail: lhlai@pku.edu.cn
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Courses：
Structural Chemistry, Biophysical Chemistry
Research Fields and Interests:
1. Structure and AI based drug design method development
2. Intrinsically disordered proteins and drug design
3. Protein allosteric regulation and drug design
4. Functional protein design
Selected Publications：
- Li, H. Y.; Zhang, C. S.; Chen, X.; You, H. T.; Lai, L. H.*, Tailoring Escherichia coli Chemotactic Sensing towards Cadmium by Computational Redesign of Ribose-Binding Protein. mSystems 7, e0108421, 2022.
- Li, Y. B.; Pei, J. F.*; Lai, L. H.* Structure-based de novo drug design using 3D deep generative models. Chem. Sci. 12, 13664-13675, 2021.
- Wang, S. W.; Sun, Q.; Xu, Y. J.; Pei, J. F.*; Lai, L. H.* A transferable deep learning approach to fast screen potential antiviral drugs against SARS-CoV-2. Brief. Bioinform. 22, bbab211, 2021.
- Sun, Q.; Ye, F.; Liang, H.; Liu, H. B.; Li, C.; Lu, R.; Huang, B.; Zhao, L.; Tan, W. J.*; Lai, L. H.*, Bardoxolone and bardoxolone methyl, two Nrf2 activators in clinical trials, inhibit SARS-CoV-2 replication and its 3C-like protease. Signal. Transduct. Target Ther. 6, 212, 2021.
- Ruan, H.; Yu, C.; Niu, X. G.; Zhang, W. L.; Liu, H. B.; Chen, L. M.; Xiong, R. Y.; Sun, Q.; Jin, C. W.; Liu, Y.; Lai, L. H.*, Computational strategy for intrinsically disordered protein ligand design leads to the discovery of p53 transactivation domain I binding compounds that activate the p53 pathway. Chem. Sci. 12, 3004-3016, 2021.
- Huang, Q. J.; Song, P. B.; Chen, Y. X.; Liu, Z. R.*; Lai, L. H.*, Allosteric Type and Pathways Are Governed by the Forces of Protein-Ligand Binding. J. Phys. Chem. Lett. 12, 5404-5412, 2021.
- Xie, J.; Lai, L. H.*, Protein topology and allostery. Curr. Opin. Struct. Biol. 62, 158-165, 2020.
- Lin, K. J.; Xu, Y. J.; Pei, J. F.*; Lai, L. H.*, Automatic retrosynthetic route planning using template-free models. Chem. Sci. 11, 3355-3364, 2020.
- Li, C.; Deng, X. B.; Zhang, W. L.; Xie, X. W.; Conrad, M.; Liu, Y.; Angeli, J. P. F.*; Lai, L. H.*, Novel Allosteric Activators for Ferroptosis Regulator Glutathione Peroxidase 4. J. Med. Chem. 62, 266-275, 2019.
- Zhou H. B.; Zhong S.; Song Z.; Zuo L. Y.; Qi Z*; Qu L. J.*; Lai L. H.*, Mechanism of DNA-induced phase separation for transcriptional repressor VRN1. Angew. Chem. Int. Ed. 58, 4858-4862, 2019.
- Xu, Y. J.; Wang, S. W.; Hu, Q. W.; Gao, S. S.; Ma, X. M.; Zhang, W. L.; Shen, Y. H.; Chen, F. J.; Lai, L. H.*; Pei, J. F.*， CavityPlus: a web server for protein cavity detection with pharmacophore modelling, allosteric site identification and covalent ligand binding ability prediction. Nucleic Acids Res. 46, W374-W379， 2018.
- Wang Q.; Liberti M. V.; Liu P.; Deng X. B.; Liu Y.; Locasale J. W.*; Lai L. H.*, Rational Design of Selective Allosteric Inhibitors of PHGDH and Serine Synthesis with Anti-tumor Activity. Cell Chem. Biol. 24, 55-65, 2017.
- Meng, H; Liu, Y*; Lai, L. H.*, Diverse Ways of Perturbing the Human Arachidonic Acid Metabolic Network To Control Inflammation. Acc. Chem. Res. 48:2242-2250, 2015.
- Pei, J. F.; Yin, N.; Ma, X. M.; Lai, L. H.*, Systems Biology Brings New Dimensions for Structure-Based Drug Design. J. Am. Chem. Soc. 136, 11556-11565, 2014.
15. Zhou, L.; Bosscher, M.; Zhang, C. S.; Ozcubukcu, S.; Zhang, L.; Zhang, W.; Li, C. J.; Liu, J. Z.; Jensen, M. P.; Lai, L. H.*; He, C.* , A protein engineered to bind uranyl selectively and with femtomolar affinity. Nature Chem. 6, 236-241, 2014.
16. Zhang, C. S.; Shen, Q.; Tang, B.; Lai, L. H.*, Computational design of helical peptides targeting TNFa. Angew. Chem. Int. Ed. Engl. 52, 11059-11062, 2013.
17. Bi, S. Y.; Yu, D. Q.; Si, G. W.; Luo, C. X.; Li, T. Q.; Ouyang, Q.; Jakovljevic, V.; Sourjik, V.; Tu, Y. H.*; Lai, L. H.*, Discovery of novel chemoeffectors and rational design of Escherichia coli chemoreceptor specificity. Proc. Natl. Acad. Sci. USA 110, 16814-16819, 2013.
18. Wu, Y. R.; He, C.; Gao, Y.; He, S.; Liu, Y.; Lai, L. H.*, Dynamic Modeling of Human 5-Lipoxygenase-Inhibitor Interactions Helps To Discover Novel Inhibitors. J. Med. Chem. 55 (6), 2597-2605, 2012.
19. Yuan, Y. X.; Pei, J. F.*; Lai, L. H.*, LigBuilder 2: A Practical de Novo Drug Design Approach. J. Chem. Inf. Model., 51 (5), 1083-1091, 2011.
20. Li, C. M.; Qi, Y. F.; Teng, X.; Yang, Z. C.; Wei, P.; Zhang, C. S.; Tan, L.; Zhou, L.; Liu, Y.; Lai, L. H.*, Maturation Mechanism of Severe Acute Respiratory Syndrome (SARS) Coronavirus 3C-like Proteinase. J. Biol. Chem. 285 (36), 28134-28140, 2010.
21. Liang, H. H.; Chen, H.; Fan, K. Q.; Wei, P.; Guo, X. R.; Jin, C. W.; Zeng, C.; Tang, C.; Lai, L. H.*, De Novo Design of a beta alpha beta Motif. Angew. Chem. Int. Ed. Engl. 48 (18), 3301-3303, 2009.
22. Yang, K.; Bai, H. J.; Qi, O. Y.; Lai, L. H.*; Tang, C., Finding multiple target optimal intervention in disease-related molecular network. Mol. Syst. Biol. 4, 228, 2008.
23. Wei, D. G.; Jiang, X. L.; Zhou, L.; Chen, J.; Chen, Z.; He, C.; Yang, K.; Liu, Y.; Pei, J. F.; Lai, L. H.*, Discovery of Multitarget Inhibitors by Combining Molecular Docking with Common Pharmacophore Matching. J. Med. Chem. 51 (24), 7882-7888, 2008.
24. Liu, S.; Liu, S. Y.; Zhu, X. L.; Liang, H. H.; Cao, A. N.; Chang, Z. J.; Lai, L. H.*, Nonnatural protein-protein interaction-pair design by key residues grafting. Proc. Natl. Acad. Sci. USA 104 (13), 5330-5335, 2007.
(=>Please see lab webpage at http://mdl.ipc.pku.edu.cn for details)
