基本信息
徐志建  男  硕导  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,曾任Journal of Chemical Information and Modeling首届青年编委,现任中国化学会计算(机)化学专业委员会委员、Frontiers in Molecular Biosciences Section副主编。主要从事分子模拟及药物设计方面的研究工作,专注于分子模拟与药物设计新方法的发展,以及这些方法在药物发现方面的应用研究。

    共发表论文100余篇,其中3篇论文的引用超过200次。申请国家发明专利50多项,软件著作权5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(Molecules 2017, 22 (9))。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。开发了基于公共空间的多模态药物-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。开发了抗新冠肺炎药物靶标预测和虚拟筛选平台D3Targets-2019-nCoV。

(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,发现了一系列活性化合物。利用计算模拟,发现用于胆囊炎、胆道炎、胆石症及胆道手术后综合征的老药柳胺酚在骨髓瘤方面的新用途,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
2017-12-31-2020-12-31,Journal of Chemical Information and Modeling ECB (Early Career Board) member,

专利与奖励

   

出版信息

(1)        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.

(2)        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.

(3)        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.

(4)        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.

(5)        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.

(6)        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

(7)        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.

(8)        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.

(9)        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.

(10)      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.

(11)      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.

(12)      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.

(13)      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.

(14)      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.

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

(16)      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.

(17)      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.

(18)      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.

(19)      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.

(20)      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.

(21)      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.

(22)      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.

(23)      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.

(24)      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.

(25)      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.

(26)      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.

(27)      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.

(28)      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.

(29)      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.

(30)      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.

(31)      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.

(32)       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