基本信息

徐志建  男  博导  中国科学院上海药物研究所
电子邮件: zjxu@simm.ac.cn
通信地址: 上海市浦东新区张江高科技园区松涛路647弄3号楼3楼
邮政编码: 201203

研究领域

    ​徐志建,中国科学院上海药物研究所研究员,博士生导师,国家优秀青年科学基金获得者(医学部),明珠菁英人才。现任中国化学会计算(机)化学专业委员会委员、上海市药学会人工智能药学专业委员会委员。主要从事药物设计理论方法研究及其在重大疾病药物研发中的应用,包括药物设计基础理论研究、软件程序开发、新化合物设计与药物合成、中药天然产物结构改造、老药新用等。

    共发表论文156篇,其中SCI论文149篇,4篇论文的引用超过200次。申请国家发明专利51项,软件著作权6件。

(1)药物-靶标结合作用的理论研究。率先在药物设计中引入卤键,首次通过计算模拟阐明卤键作用与化合物成药性的关系,阐明了卤键作用的本质,帮助人们进一步理解IUPAC的卤键定义。在卤键方面的研究工作被得克萨斯大学Mahesh Narayan教授评价为教科书式的工作,也被认为是最详实的计算工作。发现晶体结构数据中的非键相互作用(卤键、氢键、离子键等)被低估。

(2)药物设计方法发展与软件开发。开发了可以处理卤键的分子对接软件D3DOCKxb,将此软件移植到国产超级计算机上,一天可虚拟筛完4200万个化合物。开发了可以分析口袋动力学性质的软件D3Pockets,可以分析口袋的稳定性、连续性与相关性,被生物技术公司购买和使用,并入选《中国药物分子设计40年发展成就》。开发了基于人工智能的多模态药物-靶标关联预测技术MultiDTI,可以关联新化学实体和新靶标到已知的异构网络。整合了基于物理和数据驱动的计算方法,构建了综合性靶标预测与虚拟筛选平台D3CARP。开发了基于深度学习的EGFR突变肺癌的用药推荐平台D3EGFR。药物设计软件平台访问量合计超200万次。

(3)应用研究。针对肿瘤及传染性疾病等重要疾病靶标蛋白开展药物设计及结构优化研究,基于计算模拟,发现了一系列活性化合物,推动完成了两项研究者发起的临床研究。发现了抗肿瘤潜在新靶标CorC和TRIP13的首个抑制剂。发现利胆老药柳胺酚在抗骨髓瘤方面的新用途、发现治疗HIV感染的老药奈非那韦在抗新冠肺炎方面的新用途,均已完成研究者发起的临床研究。


招生信息

招生专业
1007Z1-药物设计学
招生方向
计算机辅助药物设计
化学信息学、分子模拟
人工智能药物设计

教育背景

2007-09--2012-06   中国科学院上海药物研究所   理学博士
2003-09--2007-07   山东大学   理学学士

工作经历

工作简历
2021-10~现在, 中国科学院上海药物研究所, 研究员
2015-10~2021-09,中国科学院上海药物研究所, 副研究员
2014-08~2015-09,中国科学院上海药物研究所, 助理研究员
2012-07~2014-07,中国科学院上海药物研究所, 博士后
社会兼职
2022-11-01-今,中国化学会计算(机)化学专业委员会, 委员
2017-12-30-2020-12-30,Journal of Chemical Information and Modeling, ECB (Early Career Board) member
2012-01-01-今,中国化学会高级会员、中国药学会高级会员、美国化学会会员、中国计算机学会会员,

专利与奖励

   

出版信息

(1)         Jintian Li, Liping Zhou, Zijian Han, Leyun Wu, Jianfang Zhang, Weiliang Zhu*, and Zhijian Xu*, Impact of Halogen Bonds on Protein–Peptide Binding and Protein Structural Stability Revealed by Computational Approaches. J. Med. Chem. 2024, 67 (6), 4782-4792.

(2)         Jianfang Zhang, Kinga Virág Gulyás, Jintian Li, Minfei Ma, Liping Zhou, Leyun Wu, Ruisheng Xiong, Mate Erdelyi, Weiliang Zhu*, Zhijian Xu*, Unexpected effect of halogenation on the water solubility of small organic compounds. Comput. Biol. Med. 2024, 108209.

(3)         Minfei Ma, Xinben Zhang, Liping Zhou, Zijian Han, Yulong Shi, Jintian Li, Leyun Wu, Zhijian Xu*, and Weiliang Zhu*, D3Rings: A Fast and Accurate Method for Ring System Identification and Deep Generation of Drug-Like Cyclic Compounds. J. Chem. Inf. Model. 2024, 64 (3), 724-736.

(4)         Yulong Shi1, Chongwu Li1, Xinben Zhang1, Cheng Peng, Peng Sun, Qian Zhang, Leilei Wu, Ying Ding*, Dong Xie*, Zhijian Xu*, Weiliang Zhu*, D3EGFR: a webserver for deep learning-guided drug sensitivity prediction and drug response information retrieval for EGFR mutation-driven lung cancer. Brief. Bioinform. 2024, 25 (3), bbae121.

(5)         Shuting Huo1, Leyun Wu1, Baoying Huang, Nan Liu, Jiewei Sun, Fei Ye, Yao Deng, Jing Chen, Likun Gong, Weiliang Zhu, Zhijian Xu*, Wenjie Tan*, Identification of the VP37 Pocket of Monkeypox Virus as a Promising Target for Pan-Orthopoxvirus Inhibitors through Virtual Screening and Antiviral Assays. Emerging Microbes & Infections, 2373309

(6)         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.

(7)         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.

(8)         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.

(9)         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.

(10)      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. 202366 (2), 1210-1220.

(11)      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. 2023153, 106515.

(12)      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. 202265 (6), 4424-4435.

(13)      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.

(14)      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.

(15)      Yongsheng Xie1, Yingcong Wang1Zhijian 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.

(16)      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.

(17)      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

(18)      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 202137 (23), 4485–4492.

(19)      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 202122 (2), 1053-1064.

(20)      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. iScience2021, 102370.

(21)      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.

(22)      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. 202060 (12), 6242-6250.

(23)      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 202010 (7), 1239-1248.

(24)      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.

(25)      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.

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

(27)      Zhengdan Zhu1, Guimin Wang1Zhijian 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.

(28)      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.

(29)      Wenqin Xiao1Zhijian 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.

(30)      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.

(31)      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.

(32)      Zhaoqiang Chen1, Guimin Wang1Zhijian 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 2016120 (34), 8784-8793.

(33)      Yisu Li1, Binbin Guo1Zhijian 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.

(34)      Guimin Wang1, Zhaoqiang Chen1Zhijian 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.

(35)      Xia Liu1Zhijian 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.

(36)      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.

(37)      Zhuo Yang1Zhijian 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.

(38)      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.

(39)      Xinhuan Chen1Zhijian 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.

(40)      Donghua Wen1Zhijian 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.

(41)      Zhengyan Zhang1Zhijian 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.

(42)      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.

(43)      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.



科研活动

   
科研项目
( 1 ) 基于E级高性能计算生物医药应用软件系统研制及应用, 参与, 国家任务, 2017-07--2020-12
( 2 ) 镁离子通道蛋白的结构和功能研究, 参与, 国家任务, 2016-07--2021-06
( 3 ) 奈非那韦抗新冠肺炎的机制与结构改造研究, 负责人, 地方任务, 2021-07--2024-06
( 4 ) 卤键在晶体结构再精修与药物设计中的应用研究, 负责人, 国家任务, 2019-01--2020-12
( 5 ) 药物设计与药物信息, 负责人, 国家任务, 2024-01--2026-12