​ (1) Theoretical study of drug-target binding affinity. We performed a case study as proof-of-concept to utilize halogen bonds to drug design and lead optimization (J. Med. Chem. 2011, 54, 5607). Found that halogen bonds could play roles not only in improving drug−target binding affinity but also in tuning ADME/T property (J. Chem. Inf. Model. 2014, 54, 69). We found that orbital and dispersion terms are essential terms to all XBs, clarifying the nature of halogen bonds (Phys. Chem. Chem. Phys. 2019, 21, 15106). We showed that noncovalent interactions are underestimated in protein data bank and could be recovered by QM/MM optimizations (J. Chem. Inf. Model. 2019, 59, 3389 & J. Med. Chem. 2022, 65, 4424).

 (2) Drug design method development and software development. We developed D3DOCKxb, which provides a practicable scoring function of halogen bonding for high throughput virtual screening. We developed D3Pockets to study the pocket dynamic properties, such as pocket stability, continuity, and correlation, which should be helpful to understanding protein function mechanism and drug design (J. Chem. Inf. Model. 2019, 59, 3353). We designed MultiDTI, which predicts drug–target interaction based on multi-modal representation learning to bridge the gap between new chemical entities and known heterogeneous network (Bioinformatics 2021, 37, 4485). We developed D3Targets-2019-nCoV for target prediction and virtual screening to combat COVID-19 (Acta Pharm Sin B 2020, 10, 1239 & Brief Bioinform 2021, 22, 1053 & Brief Bioinform 2022, 23, bbac147). Furthermore, we developed D3CARP, a comprehensive platform with multiple-conformation based docking, ligand similarity search and deep learning approaches for target prediction and virtual screening (Comput. Biol. Med. 2023, 164, 107283).

(3) Applied research. We carried out drug design on key potential drug targets from tumors and infectious diseases. The first inhibitor against the potential targets CorC and TRIP13 was identified (iScience 2021, 24, 102370 & Cancer Res. 2020, 80, 536). We predicted and facilitated the completion of investigator-initiated clinical studies of two drugs. Osalmid was repositioned as an inhibitor of RRM2, showing efficacy in multiple myeloma clinical trials (Biochem. Pharmacol. 2016, 103, 118 & J. Biomed. Sci. 2022, 29, 32). Nelfinavir, an FDA approved drug for the treatment of HIV infection, showed preventive and therapeutic benefits in rhesus macaques and human beings infected with SARS-CoV-2 (Signal Transduction and Targeted Therapy 2023, 8 (1), 169).

（1）        Yulong Shi¹, Xinben Zhang¹, Yanqing Yang¹, Tingting Cai, Cheng Peng, Leyun Wu, Liping Zhou, Jiaxin Han, Minfei Ma, Weiliang Zhu*, Zhijian Xu*, D3CARP: a comprehensive platform with multiple-conformation based docking, ligand similarity search and deep learning approaches for target prediction and virtual screening. Comput. Biol. Med. 2023, 164, 107283.

（2）        Liping Zhou, Jintian Li, Yulong Shi, Leyun Wu, Weiliang Zhu* and  Zhijian Xu*, Preferred microenvironments of halogen bonds and hydrogen bonds revealed using statistics and QM/MM calculation studies. Phys. Chem. Chem. Phys. 2023, 25 (26), 17692-17699.

（3）        Leyun Wu¹, Guangpu Wang¹, Liping Zhou¹, Mengxia Mo, Yulong Shi, Bo Li, Leimiao Yin, Qiang Zhao, Yongqing Yang, Chengkun Wu*, Zhijian Xu*, Weiliang Zhu*, Molecular dynamics study on the behavior and binding mechanism of target protein Transgelin-2 with its agonist TSG12 for anti-asthma drug discovery. Comput. Biol. Med. 2023, 153, 106515.

（4）        Zhijian Xu¹, Danrong Shi¹, Jian-Bao Han¹, Yun Ling¹, Xiangrui Jiang¹, Xiangyun Lu¹, Chuan Li, Likun Gong, Guangbo Ge, Yani Zhang, Yi Zang, Tian-Zhang Song, Xiao-Li Feng, Ren-Rong Tian, Jia Ji, Miaojin Zhu, Nanping Wu, Chunhui Wu, Zhen Wang, Yechun Xu, Cheng Peng, Min Zheng, Junling Yang, Feifei Du, Junliang Wu, Peipei Wang, Jingshan Shen^*, Jianliang Zhang^*, Yong-Tang Zheng^*, Hangping Yao^* & Weiliang Zhu^*. Preventive and therapeutic benefits of nelfinavir in rhesus macaques and human beings infected with SARS-CoV-2. Signal Transduction and Targeted Therapy 2023, 8 (1), 169.

（5）        Yujing Zhou, Peng Lei, Jiaxin Han, Zhiming Wang, Aiyan Ji, Yuyang Wu, Lingling Zheng, Xiaoqing Zhang, Chunrong Qu, Jian Min, Weiliang Zhu, Zhijian Xu*, Xingdang Liu*, Hao Chen*, and Zhen Cheng*, Development of a Novel 18F-Labeled Probe for PET Imaging of Estrogen Receptor β. J. Med. Chem. 2023, 66 (2), 1210-1220.

（6）        Leyun Wu¹, Guangpu Wang¹, Liping Zhou¹, Mengxia Mo, Yulong Shi, Bo Li, Leimiao Yin, Qiang Zhao, Yongqing Yang, Chengkun Wu*, Zhijian Xu*, Weiliang Zhu*, Molecular dynamics study on the behavior and binding mechanism of target protein Transgelin-2 with its agonist TSG12 for anti-asthma drug discovery. Comput. Biol. Med. 2023, 153, 106515.

（7）        Kaijie Mu, Zhengdan Zhu, Amina Abula, Cheng Peng, Weiliang Zhu^*, Zhijian Xu^*, Halogen bonds exist between noncovalent ligands and natural nucleic acids. J. Med. Chem. 2022, 65 (6), 4424-4435.

（8）        Leyun Wu¹, Liping Zhou¹, Mengxia Mo¹, Tingting Liu¹, Chengkun Wu¹, Chunye Gong, Kai Lu, Likun Gong^*, Weiliang Zhu^*, Zhijian Xu^*, SARS-CoV-2 Omicron RBD shows weaker binding affinity than the currently dominant Delta variant to human ACE2. Signal Transduction and Targeted Therapy 2022, 7 (1), 8.

（9）        Liping Zhou¹, Tingting Liu¹, Mengxia Mo¹, Yulong Shi, Leyun Wu, Yishui Li, Qiuping Qin, Weiliang Zhu^*, Chengkun Wu^*, Likun Gong^*, Zhijian Xu^*, Exploring the Binding Affinity and Mechanism between ACE2 and the Trimers of Delta and Omicron Spike Proteins by Molecular Dynamics Simulation and Bioassay. J. Chem. Inf. Model. 2022, 62 (18), 4512-4522.

（10）      Yongsheng Xie¹, Yingcong Wang¹, Zhijian Xu¹, Yumeng Lu, Dongliang Song, Lu Gao, Dandan Yu, Bo Li, Gege Chen, Hui Zhang, Qilin Feng, Yong Zhang, Ke Hu, Cheng Huang, Yu Peng, Xiaosong Wu, Zhiyong Mao, Jimin Shao^*, Weiliang Zhu^*, Jumei Shi^*, Preclinical validation and phase I trial of 4-hydroxysalicylanilide, targeting ribonucleotide reductase mediated dNTP synthesis in multiple myeloma. J. Biomed. Sci. 2022, 29 (1), 32.

（11）      Jiaxin Han¹, Tingting Liu¹, Xinben Zhang¹, Yanqing Yang¹, Yulong Shi, Jintian Li, Minfei Ma, Weiliang Zhu^*, Likun Gong^*, Zhijian Xu^*, D3AI-Spike: A deep learning platform for predicting binding affinity between SARS-CoV-2 spike Receptor Binding Domain with multiple amino acid mutations and human angiotensin-converting enzyme 2. Comput. Biol. Med. 2022, 106212.

（12）      Leyun Wu¹, Cheng Peng¹, Yanqing Yang, Yulong Shi, Liping Zhou, Zhijian Xu^*, Weiliang Zhu^*, Exploring the immune evasion of SARS-CoV-2 variant harboring E484K by molecular dynamics simulations. Briefings in Bioinformatics 2022, 23 (1). DOI: https://doi.org/10.1093/bib/bbab383

（13）      Deshan Zhou, Zhijian Xu*, Wentao Li, Xiaolan Xie*, Shaoliang Peng*, MultiDTI: Drug-target interaction prediction based on multi-modal representation learning to bridge the gap between new chemical entities and known heterogeneous network. Bioinformatics 2021. 37 (23), 4485–4492.

（14）      Yanqing Yang¹, Zhengdan Zhu¹, Xiaoyu Wang¹, Xinben Zhang¹, Kaijie Mu, Yulong Shi, Cheng Peng, Zhijian Xu*, Weiliang Zhu*, Ligand-based approach for predicting drug targets and for virtual screening against COVID-19. Briefings in Bioinformatics 2021, 22 (2), 1053-1064.

（15）      Yichen Huang¹, Kaijie Mu¹, Xinyu Teng¹, Yimeng Zhao, Yosuke Funato, Hiroaki Miki, Weiliang Zhu, Zhijian Xu*, Motoyuki Hattori*, Identification and mechanistic analysis of an inhibitor of the CorC Mg2+ transporter. iScience. 2021, 102370.

（16）      Cheng Peng¹, Zhengdan Zhu¹, Yulong Shi, Xiaoyu Wang, Kaijie Mu, Yanqing Yang, Xinben Zhang, Zhijian Xu*, Weiliang Zhu*, Computational Insights into the Conformational Accessibility and Binding Strength of SARS-CoV-2 Spike Protein to Human Angiotensin-Converting Enzyme 2. J. Phys. Chem. Lett. 2020, 11 (24), 10482-10488.

（17）      Amina Abula, Zhijian Xu*, Zhengdan Zhu, Cheng Peng, Zhaoqiang Chen, Weiliang Zhu*, Haji Akber Aisa*, Substitution Effect of the Trifluoromethyl Group on the Bioactivity in Medicinal Chemistry: Statistical Analysis and Energy Calculations. J. Chem. Inf. Model. 2020, 60 (12), 6242-6250.

（18）      Yulong Shi¹, Xinben Zhang¹, Kaijie Mu¹, Cheng Peng¹, Zhengdan Zhu, Xiaoyu Wang, Yanqing Yang, Zhijian Xu*, Weiliang Zhu*, D3Targets-2019-nCoV: a webserver for predicting drug targets and for multi-target and multi-site based virtual screening against COVID-19. Acta Pharm Sin B 2020, 10 (7), 1239-1248.

（19）      王晓宇,彭诚,杨延青,石禹龙,朱正诞,穆凯洁,李慧玉*,徐志建*,朱维良*.抗致病性冠状病毒活性化合物及其潜在靶标蛋白研究进展[J].药学学报, 2020, 55(10), 2340-2357.

（20）      Zhengdan Zhu, Zhijian Xu*, Weiliang Zhu*, Interaction Nature and Computational Methods for Halogen Bonding: A Perspective. J. Chem. Inf. Model. 2020. 60 (6), 2683-2696.

（21）      Zhijian Xu*, Qian Zhang, Jiye Shi, Weiliang Zhu*, Underestimated noncovalent interactions in Protein Data Bank. J. Chem. Inf. Model. 2019, 59 (8), 3389-3399.

（22）      Zhengdan Zhu¹, Guimin Wang¹, Zhijian Xu^*, Zhaoqiang Chen, Jinan Wang, Jiye Shi and Weiliang Zhu^*, Halogen bonding in differently charged complexes: basic profile, essential interaction terms and intrinsic sigma-hole. Phys. Chem. Chem. Phys. 2019, 21 (27), 15106-15119.

（23）      Zhaoqiang Chen¹, Xinben Zhang¹, Cheng Peng, Jinan Wang, Zhijian Xu^*, Kaixian Chen, Jiye Shi^*, Weiliang Zhu^*, D3Pockets: A Method and Web Server for Systematic Analysis of Protein Pocket Dynamics. J. Chem. Inf. Model. 2019, 59 (8), 3353-3358.

（24）      Wenqin Xiao¹, Zhijian Xu¹, Shuaikang Chang¹, Bo Li, Dandan Yu, Huiqun Wu, Yongsheng Xie, Yingcong Wang, Bingqian Xie, Xi Sun, Yuanyuan Kong, Xiucai Lan, Wenxuan Bu, Gege Chen, Lu Gao, Xiaosong Wu, Jumei Shi^*, Weiliang Zhu^*, Rafoxanide, an organohalogen drug, triggers apoptosis and cell cycle arrest in multiple myeloma by enhancing DNA damage responses and suppressing the p38 MAPK pathway. Cancer Lett. 2019, 444, 45-59.

（25）      Qian Zhang, Zhijian Xu^*, Shi Jiye, and Weiliang Zhu^*, Underestimated Halogen Bonds Forming with Protein Backbone in Protein Data Bank. J. Chem. Inf. Model. 2017, 57, 1529-1534.

（26）      Qian Zhang, Zhijian Xu^*, and Weiliang Zhu^*, The Underestimated Halogen Bonds Forming with Protein Side Chains in Drug Discovery and Design. J. Chem. Inf. Model. 2017, 57, 22-26.

（27）      Zhaoqiang Chen¹, Guimin Wang¹, Zhijian Xu^*, Jinan Wang, Yuqi Yu, Tingting Cai, Qiang Shao, Jiye Shi^*, and Weiliang Zhu^*, How do Distance and Solvent Affect the Halogen Bonding Involving Negatively Charged Donors? J. Phys. Chem. B 2016, 120 (34), 8784-8793.

（28）      Yisu Li¹, Binbin Guo¹, Zhijian Xu^*, Bo Li, Tingting Cai, Xinben Zhang, Yuqi Yu, Heyao Wang^*, Jiye Shi, Weiliang Zhu^*, Repositioning organohalogen drugs: a case study for identification of potent B-Raf V600E inhibitors via docking and bioassay. Scientific Reports 2016, 6, 31074.

（29）      Guimin Wang¹, Zhaoqiang Chen¹, Zhijian Xu^*, Jinan Wang, Yang Yang, Tingting Cai, Jiye Shi^*, Weiliang Zhu^*, Stability and Characteristics of the Halogen Bonding Interaction in an Anion-Anion Complex: A Computational Chemistry Study. J. Phys. Chem. B 2016, 120 (4), 610-620.

（30）      Xia Liu¹, Zhijian Xu¹, Chuanwei Hou¹, Meng Wang, Xinhuan Chen, Qinghui Lin, Rui Song,Meng Lou, Lijun Zhu, Yunqing Qiu, Zhi Chen, Chunhao Yang^*, Weiliang Zhu^*, Jimin Shao^*, Inhibition of hepatitis B virus replication by targeting ribonucleotide reductase M2 protein. Biochem. Pharmacol. 2016, 103, 118-128.

（31）      Yang Yang, Zhijian Xu*, Zhengyan Zhang, Zhuo Yang, Yingtao Liu, Jinan Wang, Tingting Cai, Shujin Li, Kaixian Chen, Jiye Shi*, Weiliang Zhu*, Like-Charge Guanidinium Pairing between Ligand and Receptor: An Unusual Interaction for Drug Discovery and Design? J. Phys. Chem. B 2015, 119(36), 11988-11997.

（32）      Zhuo Yang¹, Zhijian Xu¹, Yingtao Liu, Jinan Wang, Jiye Shi^*, Kaixian Chen, and Weiliang Zhu^*, Unstable, metastable, or stable halogen bonding interaction involving negatively charged donors? A statistical and computational chemistry study. J. Phys. Chem. B 2014, 118(49), 14223-14233.

（33）      Zhijian Xu¹, Zhuo Yang¹, Yingtao Liu, Yunxiang Lu^*, Kaixian Chen, Weiliang Zhu^*, Halogen Bond: Its Role beyond Drug-Target Binding Affinity for Drug Discovery and Development. J. Chem. Inf. Model. 2014, 54(1), 69-78.

（34）      Xinhuan Chen¹, Zhijian Xu¹, Lingna Zhang¹, Hongchuan Liu,Xia Liu, Meng Lou, Lijun Zhu, Bingding Huang, CaiGuang Yang, Weiliang Zhu^*, and Jimin Shao^*, The conserved Lys-95 charged residue cluster is critical for the homodimerization and enzyme activity of human ribonucleotide reductase small subunit M2. J. Biol. Chem. 2014, 289(2), 909-920.

（35）      Donghua Wen¹, Zhijian Xu¹, Li Xia¹, Xinyi Liu, Yaoyao Tu, Hu Lei, Weiwei Wang, Tongdan Wang, Lili Song, Chunmin Ma, Hanzhang Xu, Weiliang Zhu, Guoqiang Chen^*, and Yingli Wu^*, Important Role of SUMOylation of Spliceosome Factors in Prostate Cancer Cells. J. Proteome Res. 2014, 13(8), 3571-3582.

（36）      Zhengyan Zhang¹, Zhijian Xu¹, Zhuo Yang, Yingtao Liu, Jin’an Wang, Qiang Shao, Shujin Li^*, Yunxiang Lu^*, Weiliang Zhu^*, The Stabilization Effect of Dielectric Constant and Acidic Amino Acids on Arginine-Arginine (Arg-Arg) Pairings: Database Survey and Computational Studies, J. Phys. Chem. B 2013, 117(17), 4827-4835.

（37）      Zhijian Xu¹, Guirui Yan¹, Gaihong Wang, Bo Li, Jianming Zhu, Peng Sun, Xiaodong Zhang, Cheng Luo, Heyao Wang^*, Weiliang Zhu^*. Combining pharmacophore, docking and substructure search approaches to identify and optimize novel B-RafV600E inhibitors. Bioorg. Med. Chem. Lett. 2012, 22(17), 5428-5437.

（38）       Zhijian Xu¹, Zheng Liu¹, Tong Chen¹, TianTian Chen, Zhen Wang, Guanghui Tian, Jing Shi, Xuelan Wang, Yunxiang Lu, Xiuhua Yan, Guan Wang, Hualiang Jiang, Kaixian Chen, Shudong Wang, Yechun Xu^*, Jingshan Shen^*, Weiliang Zhu^*. Utilization of Halogen Bond in Lead Optimization: a Case Study of Rational Design of Potent Phosphodiesterase Type 5 (PDE5) Inhibitors. J. Med. Chem. 2011, 54(15), 5607-5611.