徐志建,中國科學院上海藥物研究所研究員,國家優青(醫學部)。現任中國化學會計算(機)化學專業委員會委員、中國化學會高級會員、中國藥學會高級會員、美國化學會會員、中國計算機學會會員。主要從事分子模擬及藥物設計方面的研究工作,專注於分子模擬與藥物設計新方法的發展,以及這些方法在藥物發現方面的套用研究。
共發表論文156篇,其中SCI論文149篇,4篇論文的引用超過200次。申請國家發明專利51項,軟體著作權6件。
基本介紹
- 中文名:徐志建
- 國籍:中國
- 民族:漢族
- 畢業院校:中國科學院上海藥物研究所
- 職業:科研
人物經歷,研究方向,主要成就,
人物經歷
2021.10起 中國科學院上海藥物研究所 研究員
2015.10 ~ 2021.9 中國科學院上海藥物研究所 副研究員
2014.8 ~ 2015.9 中國科學院上海藥物研究所 助理研究員
2012.7 ~ 2014.7 中國科學院上海藥物研究所 博士後 合作導師:陳凱先院士
2007.9~ 2012.6 中國科學院上海藥物研究所 藥物設計學理學博士 導師:朱維良研究員
研究方向
藥物-靶標的非鍵相互作用,活性化合物發現,靶標預測,抗原-抗體模擬
主要成就
(1)藥物-靶標結合作用的理論研究。率先在藥物設計中引入鹵鍵,首次通過計算模擬闡明鹵鍵作用與化合物成藥性的關係,闡明了鹵鍵作用的本質,幫助人們進一步理解IUPAC的鹵鍵定義。在鹵鍵方面的研究工作被德克薩斯大學Mahesh Narayan教授評價為教科書式的工作(Molecules 2017, 22 (9))。發現晶體結構數據中的非鍵相互作用(鹵鍵、氫鍵、離子鍵等)被低估。
(2)藥物設計方法發展與軟體開發。開發了可以處理鹵鍵的分子對接軟體D3DOCKxb,將此軟體移植到國產超級計算機上,一天可虛擬篩完4200萬個化合物。開發了可以分析口袋動力學性質的軟體D3Pockets,可以分析口袋的穩定性、連續性與相關性。開發了基於公共空間的多模態藥物-靶標關聯預測技術MultiDTI,可以關聯新化學實體和新靶標到已知的異構網路。開發了抗新冠肺炎藥物靶標預測和虛擬篩選平台D3Targets-2019-nCoV。
(3)套用研究。針對腫瘤及傳染性疾病等重要疾病靶標蛋白開展藥物設計及結構最佳化研究,發現了一系列活性化合物。研究了新冠病毒刺突蛋白的動態構象變化,揭示了RBD結構域及全長蛋白與ACE2親和力差異的分子機制。在原子水平上研究了新冠病毒刺突蛋白上的E484K突變引起免疫逃逸的分子機制,並預測了4個可能產生免疫逃逸的潛在新突變。
承擔科研項目情況:
(1) 國家自然科學基金面上項目,鹵鍵在晶體結構再精修與藥物設計中的套用研究, 2019/01~2020/12,25萬元,已結題,主持。
(2) 國家重點研發計畫“高性能計算”重點專項,基於E級高性能計算生物醫藥套用軟體系統研製及套用,2017/07 ~2020/12,749萬元,在研,參加。
(3) 國家重點研發計畫青年科學家項目,鎂離子通道蛋白的結構和功能研究, 2016/07~2021/06,500萬元,在研,參加。
(4) 國家自然科學基金青年基金,基於虛擬活性譜的藥物重定位研究,2014/01~2016/12,23萬元,已結題,主持。
(5) 人事部中國博士後第7批特別資助,基於鹵鍵的藥物重定位研究,2014/04~2015/07,15萬元,已結題,主持。
(6) 人事部中國博士後54批面上資助,鹵鍵調節藥物代謝作用的研究,2013/06~2014/07,5萬元,已結題,主持。
(7) “重大新藥創製”科技重大專項,基於B-Raf激酶V600E突變體的抗腫瘤候選藥物研究,2013/01~2015/12,108.46萬元,已結題,參加。863,新藥研發與蛋白質摺疊數值模擬軟體系統及套用, 2012/01 ~2015/12,939萬元,已結題,參加。
代表論著:
(1) LeyunWu, Cheng Peng, Yanqing Yang, Yulong Shi, Liping Zhou, ZhijianXu, Weiliang Zhu, Exploring the immune evasion ofSARS-CoV-2 variant harboring E484K by molecular dynamics simulations. Briefingsin Bioinformatics 2021
(2) Deshan Zhou, Zhijian Xu*, Wentao Li, Xiaolan Xie*,Shaoliang Peng*, MultiDTI: Drug-target interaction prediction based on multi-modalrepresentation learning to bridge the gap between new chemical entities andknown heterogeneous network. Bioinformatics 2021.
(3) Yanqing Yang, Zhengdan Zhu, Xiaoyu Wang, Xinben Zhang, Kaijie Mu, Yulong Shi, ChengPeng, Zhijian Xu*, Weiliang Zhu*,Ligand-based approach for predicting drug targets and for virtual screeningagainst COVID-19. Briefings in Bioinformatics 2021, 22(2), 1053-1064.
(4) Yichen Huang, Kaijie Mu, Xinyu Teng, Yimeng Zhao, Yosuke Funato,Hiroaki Miki, Weiliang Zhu, Zhijian Xu*,Motoyuki Hattori*, Identification and mechanistic analysis of an inhibitor ofthe CorC Mg2+ transporter. iScience. 2021, 102370.
(5) Cheng Peng, Zhengdan Zhu, Yulong Shi, Xiaoyu Wang,Kaijie Mu, Yanqing Yang, Xinben Zhang, ZhijianXu*, Weiliang Zhu*, Computational Insights into the ConformationalAccessibility and Binding Strength of SARS-CoV-2 Spike Protein to HumanAngiotensin-Converting Enzyme 2. J. Phys. Chem. Lett. 2020, 11(24), 10482-10488.
(6) Amina Abula, Zhijian Xu*, Zhengdan Zhu, Cheng Peng,Zhaoqiang Chen, Weiliang Zhu*, Haji Akber Aisa*, Substitution Effect of theTrifluoromethyl Group on the Bioactivity in Medicinal Chemistry: StatisticalAnalysis and Energy Calculations. J. Chem. Inf. Model. 2020, 60(12), 6242-6250.
(7) Yulong Shi, Xinben Zhang, Kaijie Mu, Cheng Peng, Zhengdan Zhu, Xiaoyu Wang,Yanqing Yang, Zhijian Xu*, WeiliangZhu*, D3Targets-2019-nCoV: a webserver for predicting drug targets and formulti-target and multi-site based virtual screening against COVID-19. ActaPharm Sin B 2020, 10 (7), 1239-1248.
(8) 王曉宇,彭誠,楊延青,石禹龍,朱正誕,穆凱潔,李慧玉*,徐志建*,朱維良*.抗致病性冠狀病毒活性化合物及其潛在靶標蛋白研究進展[J].藥學學報,2020, 55(10), 2340-2357.
(9) Zhengdan Zhu, Zhijian Xu*, Weiliang Zhu*, InteractionNature and Computational Methods for Halogen Bonding: A Perspective. J.Chem. Inf. Model. 2020. 60 (6), 2683-2696.
(10) Zhijian Xu*,Qian Zhang, Jiye Shi, Weiliang Zhu*, Underestimated noncovalent interactions inProtein Data Bank. J. Chem. Inf. Model. 2019, 59 (8),3389-3399.
(11) ZhengdanZhu, Guimin Wang, Zhijian Xu,Zhaoqiang Chen, Jinan Wang, Jiye Shi and Weiliang Zhu, Halogen bonding indifferently charged complexes: basic profile, essential interaction terms andintrinsic sigma-hole. Phys. Chem. Chem. Phys. 2019, 21(27), 15106-15119.
(12) ZhaoqiangChen, Xinben Zhang, Cheng Peng, Jinan Wang, Zhijian Xu, Kaixian Chen, Jiye Shi, Weiliang Zhu,D3Pockets: A Method and Web Server for Systematic Analysis of Protein PocketDynamics. J. Chem. Inf. Model. 2019, 59 (8), 3353-3358.
(13) Wenqin Xiao, Zhijian Xu,Shuaikang Chang, 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 inmultiple myeloma by enhancing DNA damage responses and suppressing the p38 MAPKpathway. Cancer Lett. 2019, 444, 45-59.
(14) QianZhang, Zhijian Xu, Shi Jiye, and WeiliangZhu, UnderestimatedHalogen Bonds Forming with Protein Backbone in Protein Data Bank. J. Chem.Inf. Model. 2017, 57,1529-1534.
(15)Qian Zhang, Zhijian Xu, and Weiliang Zhu, The UnderestimatedHalogen Bonds Forming with Protein Side Chains in Drug Discovery and Design. J. Chem. Inf. Model. 2017, 57, 22-26.
(16)Zhaoqiang Chen, Guimin Wang, Zhijian Xu,Jinan Wang, Yuqi Yu, Tingting Cai, Qiang Shao, Jiye Shi, and Weiliang Zhu, How do Distance and SolventAffect the Halogen Bonding Involving Negatively Charged Donors? J. Phys.Chem. B 2016, 120 (34),8784-8793.
(17) YisuLi, Binbin Guo, Zhijian Xu,Bo Li, Tingting Cai, Xinben Zhang, Yuqi Yu, Heyao Wang, Jiye Shi, Weiliang Zhu, Repositioning organohalogendrugs: a case study for identification of potent B-Raf V600E inhibitors viadocking and bioassay. Scientific Reports 2016, 6, 31074.
(18) GuiminWang, Zhaoqiang Chen, Zhijian Xu, Jinan Wang, Yang Yang, Tingting Cai, JiyeShi, Weiliang Zhu, Stability and Characteristics of theHalogen Bonding Interaction in an Anion-Anion Complex: A ComputationalChemistry Study. J. Phys. Chem. B 2016, 120 (4), 610-620.
(19) Xia Liu, Zhijian Xu,Chuanwei Hou, Meng Wang, Xinhuan Chen, Qinghui Lin, Rui Song,MengLou, Lijun Zhu, Yunqing Qiu, Zhi Chen, Chunhao Yang, Weiliang Zhu,Jimin Shao, Inhibition of hepatitis B virus replication bytargeting ribonucleotide reductase M2 protein. Biochem. Pharmacol. 2016,103, 118-128.
(20)Yang Yang, Zhijian Xu*, Zhengyan Zhang, Zhuo Yang, Yingtao Liu, Jinan Wang, Tingting Cai,Shujin Li, Kaixian Chen, Jiye Shi*, Weiliang Zhu*, Like-Charge GuanidiniumPairing between Ligand and Receptor: An Unusual Interaction for Drug Discoveryand Design? J. Phys. Chem. B 2015,119(36), 11988-11997.
(21) Zhuo Yang, Zhijian Xu,Yingtao Liu, Jinan Wang, Jiye Shi, Kaixian Chen, and Weiliang Zhu,Unstable, metastable, or stable halogen bonding interaction involvingnegatively charged donors? A statistical and computational chemistry study. J. Phys. Chem. B2014, 118(49), 14223-14233.
(22) ZhijianXu, Zhuo Yang, Yingtao Liu, Yunxiang Lu,Kaixian Chen, Weiliang Zhu, Halogen Bond: Its Role beyondDrug-Target Binding Affinity for Drug Discovery and Development. J. Chem.Inf. Model. 2014,54(1),69-78.
(23) Xinhuan Chen, Zhijian Xu,Lingna Zhang, Hongchuan Liu,Xia Liu, Meng Lou, Lijun Zhu, BingdingHuang, CaiGuang Yang, Weiliang Zhu, and Jimin Shao, Theconserved Lys-95 charged residue cluster is critical for the homodimerizationand enzyme activity of human ribonucleotide reductase small subunit M2. J.Biol. Chem. 2014,289(2),909-920.
(24) Donghua Wen, Zhijian Xu,Li Xia, Xinyi Liu, Yaoyao Tu, Hu Lei, Weiwei Wang, Tongdan Wang, LiliSong, Chunmin Ma, Hanzhang Xu, Weiliang Zhu, Guoqiang Chen, andYingli Wu, Important Role of SUMOylation of Spliceosome Factors inProstate Cancer Cells. J. Proteome Res. 2014,13(8), 3571-3582.
(25) Zhengyan Zhang, Zhijian Xu,Zhuo Yang, Yingtao Liu, Jin’an Wang, Qiang Shao, Shujin Li,Yunxiang Lu, Weiliang Zhu, The Stabilization Effect ofDielectric Constant and Acidic Amino Acids on Arginine-Arginine (Arg-Arg)Pairings: Database Survey and Computational Studies, J. Phys. Chem. B2013,117(17), 4827-4835.
(26) Zhijian Xu,Guirui Yan, GaihongWang, 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 novelB-RafV600E inhibitors. Bioorg. Med. Chem.Lett. 2012,22(17), 5428-5437.
(27) ZhijianXu,Zheng Liu, Tong Chen, 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 Bondin Lead Optimization: a Case Study of Rational Design of PotentPhosphodiesterase Type 5 (PDE5) Inhibitors. J. Med. Chem. 2011,54(15), 5607-5611.