徐锡明 | 博士 | 副研究员 | 硕士生导师 | |
科室: | 海洋创新药物筛选与评价平台 | |||
办公电话: | 0532-85902578 | 电子邮箱: | xuximing@ouc.edu.cn | |
联系地址: | 山东省青岛市香港东路23号青岛海洋生物医药研究院C301 | |||
研究方向: | 1.基于结构的海洋药物发现和设计 2海洋结构药理学 3. 分子对接方法研究 | |||
个人简介 | ||||
主要从事基于结构的海洋药物药物发现和设计,以及结构药理学研究,通过计算机辅助、生化模型,细胞模型等多尺度跨学科进行海洋药物筛选,以结构为重点,从构象、相互作用、水环境等进行设计,研究精准的分子对接方法,开发watvina分子对接工具。近年来在PNAS等杂志上发表论文30余篇,主持国家自然科学基金、山东省重点研发计划子课题等项目。 | ||||
教育背景 | ||||
2010.09~2014.09 | 法国巴黎第七大学功能与适应生物学部 | 生物化学 | 博士 | |
2007.09~2010.06 | 兰州大学生命科学学院 | 生物物理 | 硕士 | |
2003.09~2007.06 | 兰州大学生命科学学院 | 生物技术 | 学士 | |
工作经历 | ||||
2018.10~今 | 中国海洋大学医药学院 | 副研究员 |
| |
2016.10~2018.09 | 江苏理工学院生物信息与医药工程研究所 | 副研究员 |
| |
2015.11~2016.09 | 法国巴黎巴斯德研究所 | 博士后 |
| |
2014.09~2015.11 | 法国巴黎心血管研究中心 | 博士后 |
| |
| ||||
承担课程 | ||||
高等药物化学(研究生课程) 计算机辅助药物设计(研究生课程) 抗体药物工程(研究生课程) 生物化学实验(本科生课程) | ||||
研究进展 | ||||
海洋天然产物具有结构复杂、获取困难、含量少等诸多成药性开发挑战,进一步在化学空间下进行优化也需要海量的计算,近年来计算硬件有了巨大发展,尤其是异构计算的发展,但分子对接的准确性依然存在着挑战,相互作用难以解释其构效关系,复杂的溶剂环境成为一个重要的突破点,蛋白质活性口袋内水分子网络的定量评估,成为实验和理论上难以解决的重要科学问题。本课题组最近在watvina分子对接软件上不断优化,提升其对构象预测的准确性,在相互作用、水分子网络、药效团等方面改进,为进一步计算结合自由能提供可靠的构象。 从技术到应用方向,课题组关注疾病及其共性来源,靶向衰老细胞是治疗各种慢性疾病的共同目标,关注促进衰老细胞死亡与抑制衰老相关分泌表型的药物发现,根据靶点结构,发现和设计海洋抗衰老药物是目前正在推进的课题,为“蓝色药库”贡献新的思路。 | ||||
| ||||
代表性论文 | ||||
[1] Zhang S, Sun Y, Yao F, Li H, Yang Y, Li X, Bai Z, Hu Y, Wang P*, Xu X*. Ginkgo Biflavones Cause p53 Wild-Type Dependent Cell Death in a Transcription-Independent Manner of p53[J]. J Nat Prod. 2023. doi:10.1021 /acs.jnatprod.2c00959. [2] Bai D, Sun Y, Li Q, Li H, Liang Y, Xu X*, Hao J*. Leonurine attenuates OVA-induced asthma via p38 MAPK/NF-κB signaling pathway[J]. Int Immunopharmacol. 2023;114:109483. [3] Yang C#, Li D#, Wang S, Xu M, Wang D, Li X, Xu X*, Li C*. Inhibitory activities of alginate phosphate and sulfate derivatives against SARS-CoV-2 in vitro[J]. Int J Biol Macromol. 2023;227:316-328. [4] Luo D#, Liu X#, Jiang L, Guo Z, Lv Y, Tian X, Wang X, Cui S, Wan S, Xu X*, Li X*, Qu X*. Rational Design, Synthesis, and Biological Evaluation of Novel S1PR2 Antagonists for Reversing 5-FU-Resistance in Colorectal Cancer[J]. J Med Chem. 2022,65(21):14553-14577. [5] Zhang S, Wang Y, Sun Y, Zhao G, Wang J, Liu L, Liu F, Wang P*, Xu X*. 4′,7-Di-O-methylnaringenin (DMNG), a naringenin derivative, activates p53 signal pathway through down-regulating MDM2[J]. Journal of Functional Foods, 2022, 89: 104962. [6] Zhang Y, Wang Y, Zhao Z, Peng W, Wang P, Xu X*, Zhao C*. Glutaminyl cyclases, the potential targets of cancer and neurodegenerative diseases[J]. European Journal of Pharmacology, 2022,931:175178. [7] Zhao G#, Liu X#, Wang S#, Bai Z, Zhang S, Wang Y, Yu H*, Xu X*, Hydrogen bonding penalty used for virtual screening to discover potent inhibitors for Papain-Like cysteine proteases of SARS-CoV-2[J].Chemical Biology & Drug Design. 2022,100(4):502-514. [8] Zhao C, Xie Y, Xu L, Ye F, Xu X, Yang W, Yang F, Guo J. Structures of a mammalian TRPM8 in closed state[J]. Nature Communications, 2022, 13(1): 3113. [9] Zhang S, Wang Y, Sun Y, Zhao G, Wang J, Liu L, Liu F, Wang P, Yang J*, Xu X*. Hinokiflavone, as a MDM2 inhibitor, activates p53 signaling pathway to induce apoptosis in human colon cancer HCT116 cells[J]. Biochemical and Biophysical Research Communications, 2022, 594: 93–100. [10] Wang J, Yu X, Ding Z J, Zhang X, Luo Y, Xu X, Xie Y, Li X, Yuan T, Zheng S J, Yang W, Guo J. Structural basis of ALMT1-mediated aluminum resistance in Arabidopsis[J]. Cell Research, 2022, 32(1): 89–98. [11] Zhang S#, Wang Y#, Liu L, Zhao G, Sun Y, Wang J, Liu F, Wang P*, Xu X*. Virtual Screening Inhibitors of Ubiquitin-specific Protease 7 combining Pharmacophore Modeling and Molecular Docking[J]. Molecular Informatics, 2022,e2100273. [12] Wang Y, Zhang S, Zhang Y, Yao F, Zhao G, Wang J, Liu L, Yang Y, Li X, Sun Y, Hu Y, Bai Z, Wang P*, Li R*, Xu X*. American Chemical Society, 2021. Screening and Evaluation of Flavonoids as Xanthine Oxidase Inhibitors for Reducing Uric Acid through Combined Cell Biology and Molecular Simulation[J]. ACS Food Science & Technology, 2021, 1(11): 2182–2191. [13] Liu X, Liu Y, Zhao G, Zhang Y, Liu L, Wang J, Wang Y, Zhang S, Li X, Guo D, Wang P*, Xu X*. Biochemical Characterization of Arylamine N-acetyltransferases From Vibrio vulnificus[J]. Frontiers in Microbiology, 2021, 11. [14] Li B, Zhou Q, Wang H, Zha Y, Zheng P, Yang T, Ma D, Qiu L, Xu X, Hu Y, Roig A, Yu S, Xue W. Mitochondria-targeted magnetic gold nanoheterostructure for multi-modal imaging guided photothermal and photodynamic therapy of triple-negative breast cancer[J]. Chemical Engineering Journal, 2021, 403. [15]Xu X#, Zhang W#, Berthelet J, Liu R, Michail C, Chaffotte A F, Dupret J-M, Rodrigues-Lima F. From transglutaminases (TGs) to arylamine N-acetyltransferases (NATs): Insight into the role of a spatially conserved aromatic amino acid position in the active site of these two families of enzymes[J]. Biochemical and Biophysical Research Communications, 2020, 525(2): 308–312. [16] Li Z, Li X, Huang Y-Y, Wu Y, Liu R, Zhou L, Lin Y, Wu D, Zhang L, Liu H, Xu X, Yu K, Zhang Y, Cui J, Zhan C-G, Wang X, Luo H-B. Identify potent SARS-CoV-2 main protease inhibitors via accelerated free energy perturbation-based virtual screening of existing drugs[J]. Proceedings of the National Academy of Sciences (PNAS), 2020, 117(44): 27381–27387. [17] Aubey F#, Corre J-P#, Kong Y#, Xu X#, Obino D, Goussard S, Lapeyrere C, Souphron J, Couturier C, Renard S, Dumenil G. Inhibitors of the Neisseria meningitidis PilF ATPase provoke type IV pilus disassembly[J]. Proceedings of the National Academy of Sciences (PNAS), 2019, 116(17): 8481–8486. [18]Xu X, Mathieu C, Berthelet J, Duval R, Linh Chi Bui, Busi F, Dupret J-M, Rodrigues-Lima F*. Human Arylamine N-Acetyltransferase 1 Is Inhibited by the Dithiocarbamate Pesticide Thiram[J]. Molecular Pharmacology, 2017, 92(3): 358–365. [19]Li S#, Wang L#, Xu X#, Lin S, Wang Y, Hao J*, Sun M*. Structure-Based Design and Synthesis of a New Phenylboronic-Modified Affinity Medium for Metalloprotease Purification[J]. Marine Drugs, 2017, 15(1). | ||||
授权专利 | ||||
1. 异噻(硒)唑酮类衍生物及其在抗冠状病毒药物中的应用(202110470383.9),位次1; | ||||
项目课题 | ||||
1. 国家自然科学基金青年项目,空间保守位点对芳香胺N-乙酰转移酶催化机制的作用(31900910),主持; | ||||
【关闭】