计算生物物理化学


药物化学生物学课题组                  
中国科学院长春应用化学研究所

吉林省长春市人民大街5625号  130022                                           

电话: 0431-85262240

手机: 17543057053

邮箱: yibo.wang@ciac.ac.cn

网页: http://medchem.ciac.jl.cn/74


工作经历

  • 副研究员，中国科学院长春应用化学研究所

吉林省长春市                                                                                               2021至今

  • 助理研究员，中国科学院长春应用化学研究所(合作者：王晓辉研究员)

吉林省长春市                                                                                               2017-2021

  • 博士后，西奈山伊坎医学院(指导教授: Dr. Marta Filizola)

纽约市，纽约，美国                                                                                   2016-2017

教育经历

  • 生物化学博士，卡尔加里大学(指导教授: Dr. Sergei Noskov)

卡尔加里，阿尔伯塔，加拿大                                                                    2011−2016

毕业论文:离子或溶质与电压门控离子通道相互作用的分子机理(04/2016)

  • 物理化学研究生，吉林大学理论化学研究所(指导教授: 黄旭日教授)

长春，吉林，中国                                                                                      2008–2011

  • 材料化学学士，吉林大学化学学院

长春，吉林，中国                                                                                      2004−2008

科研经验

  • 运用Markov State Model进行生物分子的动力学特性分析
  • 使用或修改分子动力学模拟软件研究生物和药物相关分子的性质；
  • 分子力场开发和使用（常规力场和极性化力场）；
  • 蛋白与配体相互识别相关的自由能计算；
  • 药物分子设计与结合位点预测；
  • 高效建立并在不同平台运行大量并行计算（CPU/GPU）；
  • 编程处理和分析数据；
  • 卓越的团队合作技能。

科研项目

目前课题（合作者: 王晓辉研究员）                                                                2017至今

  • Toll样受体的天然免疫识别机理：

天然免疫系统中的Toll样受体通过特异性地识别进入机体的病原体所特有的保守结构，启动天然免疫系统，产生炎症免疫反应，在自身免疫疾病、癌症、心血管疾病、神经病理性疼痛及药物成瘾方面发挥关键作用。课题组针对Toll样受体对外源物的识别机理展开研究，为相关疾病的药物发现提供理论依据。

博士后期间(指导教师: Dr. Marta Filizola)                                                        2016-2017

  • GPCR蛋白的离子调控机理：

G 蛋白偶联受体(GPCR)是一类膜蛋白受体的总称。其控制细胞内外信号通路的重要作用，使它成为现代药物的重要靶点。本人借助分子动力学模拟，从热力学和动力学两方面揭示钠离子调控GPCR 与配体结合的分子机理。

博士期间(指导教师: Dr. Sergei Noskov)                                                          2011−2016

  • 常规力场和极性化力场下离子通道的离子选择性研究：

离子通道是位于细胞膜内的控制离子进出细胞的膜蛋白。本人使用BlueGene和其他高性能计算机群，通过自由能微扰和平均力势计算，重建一维和二维自由能图，揭示了离子通道的离子选择机理。.

  • 抗心律失常或抗真菌药物分子设计及其与人类离子通道的相互作用：

许多用于维持窦性心律或抗真菌药物会阻塞人类钾离子通道进而导致严重的副作用，其中包括眩晕甚至猝死。为优化现有药物，本人使用Schrödinger模块建立一个类药物分子库。借助于Schrödinger，Gold 和AutoDock进行高通量筛选、刚性或柔性对接以及受体柔性对接，缩小候选药物范围。通过平均力势的计算，候选药物及现有药物的亲和力得以量化，结合路径得以重现。

研究生期间(指导教师: 黄旭日教授)                                                                2008−2011

  • 小分子释放或转运路径研究:

生物体中小分子沿其特有路径从配体转运蛋白中释放或转运。本人设计了一个新的方案搜索小分子释放路径并研究其过程中与蛋白的相互作用。

获奖情况:

  • Faculty of Graduate Studies Travel Award                                                        03/2016
  • Graduate Research Scholarship                                                                          01/2016
  • Eyes High International Doctoral Scholarship                                                        09/2015
  • Eyes High International Doctoral Scholarship                                                        09/2014
  • Bettina Bahlsen Memorial Graduate Scholarship                                                    09/2014
  • Graeme Bell and Norma Kay Sullivan-Bell Graduate Scholarship                   09/2012
  • 国家奖学金                                                                    09/2010
  • 研究生新生入学奖学金                                                       09/2010
  • 研究生杰出人才培养资助计划                                        10/2010
  • 国家奖学金                                                                    09/2009
  • 研究生一等奖学金                                                                                          09/2009

研究技能

  • 编程语言: FORTRAN 77, Python, C-shell scripting
  • 软件使用: CHARMM, NAMD, Gromacs, Gaussian, Schrödinger, Gold, AutoDock, PyEMMA.
  • 计算方法：
  • Markov State Model建立与分析；

蛋白与配体自由能计算与分解；

拉伸动力学研究配体释放；

伞形取样(Umbrella Sampling)或副本(Replica Exchange)交换计算平均力势；

自由能微扰预测配体亲和性。

发表文章: ($共同一作, IF: Impact Factor for 2015)

  1. Wang, X.; Lin, C.; Wu, S.; Zhang, T.; Wang, Y.; Jiang, Y.; Wang, X., Cannabidivarin alleviates neuroinflammation by targeting TLR4 co-receptor MD2 and improves morphine-mediated analgesia. Frontiers in Immunology 2022, 13, 929222
  2. Li, Y.; Wang, Y.; Lu, L.; Shi, J.; Wang, X., Non-small molecule therapeutics for drug addiction: from pharmacokinetics modulating to synthetic biology. Fundamental Research 2022, Doi:10.1016/j.fmre.2022.09.027
  3. Wang, Y.; Zhang, C.; Tang, K.; Wang, X., En route for molecular dynamics simulation of a living cell. Fundamental Research 2022, Doi:10.1016/j.fmre.2022.06.002
  4. Mustafa, S.; Evans, S.; Barry, B.; Barratt, D.; Wang, Y.; Lin, C.; Wang, X.; Hutchinson, M., Toll-like receptor 4 in pain: bridging molecules-to-cells-to-systems. Handbook of Experimental Pharmacology 2022, 276, 239-273
  5. You, Y.; Deng, Q.; Wang, Y.; Sang, Y.; Li, G.; Pu, F.; Ren, J.; Qu, X., DNA-based platform for efficient and precisely targeted bioorthogonal catalysis in living systems. Nature communications 2022, 13 (1), 1459
  6. Zhao, J.; Xu, Y.; Ma, S.; Wang, Y.; Huang, Z.; Qu, H.; Yao, H.; Zhang, Y.; Wu, G.; Huang, L.; Song, W.; Tang, Z.; Chen, X., A minimalist binary vaccine carrier for personalized postoperative cancer vaccine therapy. Advanced Materials 2022, 34 (10), 2109254
  7. Wu, S.; Lin, C.; Zhang, T.; Zhang, B.; Jin, Y.; Wang, H.; Li, H.; Wang, Y.; Wang, X., Pentamidine alleviates inflammation and lipopolysaccharide-induced sepsis by inhibiting TLR4 activation via targeting MD2. Frontiers in Pharmacology 2022, 13, 835081
  8. You, Y.; Liu, H.; Zhu, J.; Wang, Y.; Pu, F.; Ren, J.; Qu, X., A DNAzyme-augmented bioorthogonal catalysis system for synergistic cancer therapy. Chemical Science 2022, 13 (26), 7829-7836
  9. Zhang, B.; Peng, Y.; Wang, Y.; Wang, X., Exploring the trimerization process of a transmembrane helix with an ionizable residue by molecular dynamics simulations: a case study of transmembrane domain 5 of LMP-1. Physical Chemistry Chemical Physics 2022, 24 (11), 7084-7092
  10. Lin, C.; Wang, H.; Zhang, M.; Mustafa, S.; Wang, Y.; Li, H.; Yin, H.; Hutchinson, M.; Wang, X., TLR4 biased small molecule modulators. Pharmacology & Therapeutics 2021, 228, 107918
  11. Wang, Y.; Wu, S.; Zhang, C.; Jin, Y.; Wang, X., Dissecting the role of N-glycan at N413 in Toll-like receptor 3 via molecular dynamics simulations. Journal of Chemical Information and Modeling 2021, 62 (21), 5258-5266
  12. Wang, S.; Wang, H.; Lin, C.; Zhang, T.; Gao, J.; Wu, S.; Wang, Y.; Li, H.; Min, W.; Liu, C.; Wang, X., Structure-activity relationship study of dihydroartemisinin C-10 hemiacetal derivatives as Toll-like receptor 4 antagonists. Bioorganic Chemistry 2021, 114, 105107
  13. Li, H.; Peng, Y.; Lin, C.; Zhang, X.; Zhang, T.; Wang, Y.; Li, Y.; Wu, S.; Wang, H.; Hutchinson, M.; Watkins, L.; Wang, X., Nicotine and its metabolite cotinine target MD2 and inhibit TLR4 signaling. The Innovation 2021, 2 (2), 100111
  14. Zhang, Y.; Zhang, X.; Lin, C.; Wu, S.; Wang, F.; Wang, H.; Wang, Y.; Peng, Y.; Hutchinson, M.; Li, H.; Wang, X., Artemisinin inhibits TLR4 signaling by targeting co-receptor MD2 in microglial BV-2 cells and prevents lipopolysaccharide-induced blood-brain barrier leakage in mice. Journal of neurochemistry 2021, 157 (3), 611-623
  15. Zhang, B.; Wang, Y.; Lin, C.; Li, H.; Wang, X.; Peng, Y.; Mineev, K.; Wilson, A.; Wang, H.; Wang, X., Targeting the transmembrane domain 5 of latent membrane protein 1 using small molecule modulators. European Journal of Medicinal Chemistry 2021, 214, 113210
  16. Wang, Y.; Zhang, B.; Lin, C.; Liu, Y.; Yang, M.; Peng, Y.; Wang, X., Dissecting role of charged residue from transmembrane domain 5 of latent membrane protein 1 via in silico simulations and wet-lab experiments. The Journal of Physical Chemistry B 2021, 125 (8), 2124-2133
  17. Zhang, X.; Wang, H.; Wang, Y.; Li, H.; Wu, S.; Gao, J.; Zhang, T.; Xie, J.; Wang, X., Nalmefene non-enantioselectively targets myeloid differentiation protein 2 and inhibits toll-like receptor 4 signaling: wet-lab techniques and in silico simulations. Physical Chemistry Chemical Physics 2021, 23 (21), 12260-12269
  18. Li, Z.; Wang, D.; Lu, J.; Huang, B.; Wang, Y.; Dong, M.; Fan, D.; Li, H.; Gao, Y.; Hou, P.; Li, M.; Liu, H.; Pan, Z.; Zheng, J.; Bai, J., Methylation of EZH2 by PRMT1 regulates its stability and promotes breast cancer metastasis. Cell Death & Differentiation 2020, 27 (12), 3226-3242
  19. Peng, Y.; Wang, Y.; Wang, X., Exploring the thermodynamics of 7-amino actinomycin D-Induced single-stranded DNA hairpin by spectroscopic techniques and computational simulations. The Journal of Physical Chemistry B 2020, 124 (45), 10007-10013
  20. Kot, E.; Wang, Y.; Goncharuk, S.; Zhang, B.; Arseniev, A.; Wang, X.; Mineev, K., Oligomerization analysis as a tool to elucidate the mechanism of EBV latent membrane protein 1 inhibition by pentamidine. Biochimica et Biophysica Acta (BBA)-Biomembranes 2020, 1862 (10), 183380
  21. Wang, Y.; Zhang, S.; Li, H.; Wang, H.; Zhang, T.; Hutchinson, M.; Yin, H.; Wang, X., Small-molecule modulators of Toll-like receptors. Accounts of Chemical Research 2020, 53 (5), 1046-1055
  22. Zhang, X.; Wang, Y.; Wang, H.; Li, H.; Zhang, T.; Peng, Y.; Wang, X., Exploring methamphetamine nonenantioselectively targeting Toll-like receptor 4/myeloid differentiation protein 2 by in silico simulations and wet-lab techniques. Journal of Chemical Information and Modeling 2020, 60 (3), 1607-1613
  23. Wang, Y.; Finol-Urdaneta, R.; Ngo, V.; French, R.; Noskov, S., Author correction: bases of bacterial sodium channel selectivity among organic cations. Scientific Reports 2019, 9 (1), 18992
  24. Peng, Y.; Zhang, X.; Zhang, T.; Grace, P.; Li, H.; Wang, Y.; Li, H.; Chen, H.; Watkins, L.; Hutchinson, M.; Yin, H.; Wang, X., Lovastatin inhibits Toll-like receptor 4 signaling in microglia by targeting its co-receptor myeloid differentiation protein 2 and attenuates neuropathic pain. Brain, behavior, and immunity 2019, 82, 432-444
  25. Zhang, X.; Peng, Y.; Grace, P.; Metcalf, M.; Kwilasz, A.; Wang, Y.; Zhang, T.; Wu, S.; Selfridge, B.; Portoghese, P.; Rice, K.; Watkins, L.; Hutchinson, M.; Wang, X., Stereochemistry and innate immune recognition: (+)-norbinaltorphimine targets myeloid differentiation protein 2 and inhibits toll-like receptor 4 signaling. The FASEB Journal 2019, 33 (8), 9577
  26. Wang, Y.; Peng, Y,; Zhang, B.; Zhang, X.; Li, H.; Wilson, A.; Mineev, K.; Wang, X., Targeting trimeric transmembrane domain 5 of oncogenic latent membrane protein 1 using a computationally designed peptide. Chemical Science 2019, 10(32), 7584-7590
  27. Wang, Y.; Finol-Urdaneta, R. K.; French, R. J.; Noskov, S. Y., Bases of sodium channel selectivity among organic cations. Scientific Reports 2019, 9(1), 15260
  28. Hu, X.; Wang, Y.; Hunkele, A.; Provasi, D.;Pasternak, G.; Filizola, M.*, Kinetic and thermodynamic insights into sodium ion translocation through the μ-opioid receptor from molecular dynamics and machine learning analysis. PLoS Computational Biology 2019, 15(1): e1006689
  29. Zhang X.; Cui, F. ; Chen, H.; Zhang, T.; Yang, K.; Wang Y.; Jiang Z.; Rice, K.C.; Watkins, L.R.; Hutchinson, M.R.; Li, Y.; Peng, Y. and Wang, X., Dissecting the Innate Immune Recognition of Opioid Inactive Isomer (+)-Naltrexone Derived Toll-like Receptor 4 (TLR4) Antagonists. Journal of Chemical Information and Modeling 2018, 58(4), 816-825
  30. Yang, P.; Perissinotti, L.; López-Redondo, F.; Wang, Y.; DeMarco, K.; Jeng, M.; Vorobyov, I; Harvey, R.; Kurokawa, J.; Noskov, S.; Clancy, C., A multiscale computational modeling approach predicts mechanisms of female sex risk in the setting of arousal-induced arrhythmias. Journal of Physiology (London) 2017, 595(14),4695-4723(IF: 4.731)
  31. Wang, Y.; Guo, J.; Perissinotti, L.; Lees-Miller, J.; Teng, G.; Durdagi, S.; Duff, H.; Noskov, S., Role of the pH in state-dependent blockade of hERG currents. Scientific Reports 2016, 6:32536. (IF: 5.228)
  32. Ngo, V.; Wang, Y.; Haas, S.; Noskov, S. Y.; Farley, R. A., K+ block is the mechanism of functional asymmetry in bacterial Nav channels. PLoS Computational Biology 2016, 12(1): e1004482. (IF: 4.587)
  33. Lees-Miller, J. P.; Guo, J.; Wang, Y.; Perissinotti, L. L.; Noskov, S. Y.; Duff, H. J., Ivabradine prolongs phase 3 of cardiac repolarization and blocks the hERG1 (KCNH2) current over a concentration-range overlapping with that required to block HCN4. Journal of Molecular and Cellular Cardiology2015, 85, 71-78. (IF:4.847)
  34. Chamberlin, A.$; Qiu, F.$; Wang, Y.$; Noskov, S. Y.; Larsson, H. P., Mapping the gating and permeation pathways in the voltage-gated proton channel Hv1. Journal of Molecular Biology2015, 427 (1), 131-145. (IF: 4.517)
  35. Wang, Y.; Chamberlin, A. C.; Noskov, S. Y., Molecular strategies to achieve selective conductance in NaK channel variants.Journal of Physical Chemistry B 2014, 118 (8), 2041-9. (IF: 3.187)
  36. Chamberlin, A.; Qiu, F.; Rebolledo, S.; Wang, Y.; Noskov, S. Y.; Larsson, H. P., Hydrophobic plug functions as a gate in voltage-gated proton channels. Proceedings of the National Academy of Sciences of the United States of America (PNAS)2014, 111 (2), E273-E282. (IF:9.423)
  37. Finol-Urdaneta, R. K.$; Wang, Y.$; Al-Sabi, A.; Zhao, C. F.; Noskov, S. Y.; French, R. J., Sodium channel selectivity and conduction: Prokaryotes have devised their own molecular strategy. Journal of General Physiology 2014, 143 (2), 157-171. (IF: 4.511)
  38. Feng, X. L.; Zhao, X.; Yu, H.; Wang, Y.; Sun, T. D.; Huang, X. R., Molecular Dynamics of an Extremely Thermophilic Ribose Binding Protein. Acta Chim Sinica 2012, 70 (5), 606-610. (IF: 1.843)
  39. Wang, Y.; Zhao, X.; Sun, B. L.; Yu, H.; Huang, X. R., Molecular dynamics simulation study of the vanillate transport channel of Opdk. Archives of Biochemistry and Biophysics 2012, 524 (2), 132-139. (IF:2.807)
  40. Wang, Y.; Zhao, X.; Yu, H.; Huang, X. R., Releasing of the chromophore from the drug delivery protein C-1027: A molecular dynamics simulations study. Journal of Structural Biology 2010, 172 (3), 284-293. (IF:2.570)

部分报告:

  • 报告:Yibo Wang, Na+ channel Study with Polarizable Force Field. The 7th Kananaskis Symposium on Molecular Simulation, Kananaskis, Canada                               02/2016
  • 海报: Yibo Wang, Laura Perissinotti, Jiqing Guo, Henry Duff, Sergei Noskov, Molecular Origins of State-dependent hERG1 Blockade by Dofetilide. The 59th BPS Annual Meeting, Baltimore, USA                                                                        02/2015
  • 海报: Yibo Wang, Adam Chamberlin, Chunfeng Zhao, Sergei Noskov, Strategies to Achieve Selective Conductance in K- and Na- Selective Ion Channels. The 58th BPS Annual Meeting, San Francisco, USA                                                                 02/2014
  • 报告:Yibo Wang, Molecular Dynamics Study of hERG Blockers. The 5th Kananaskis Symposium on Molecular Simulation, Kananaskis, Canada                                02/2014
  • 受邀报告: Yibo Wang, Study of Three Typical Ion Channels via Molecular Dynamics. Telluride Workshop: Biophysics of ion Channels, Telluride, USA                     07/2013
  • 报告:Yibo Wang, Molecular Mechanism Study of Mutant NaK Channels. The 4th Kananaskis Symposium on Molecular Simulation, Kananaskis, Canada              01/2013
  • 海报:Yibo Wang, Chunfeng Zhao, Rocio Finol-Urdaneta, Sergei Noskov, Robert French, Functional Study of the Sodium Ion Channel Permeation with Molecular Simulations.CSHAsia 2012 Conference, Suzhou, China                                     09/2012

杂志评审:

Biophysical Journal, BMC Pharmacology and Toxicology, PLOS Computational Biology, Current Topics in Membranes, Journal of Biomolecular Structure & Dynamics, Journal of Molecular Modeling, Journal of Theoretical and Computational Chemistry

教学经验:

  • BCEM 553: 分子生物物理学 (Dr. Sergei Noskov)                                              2015
  • BCEM 577: 生物分子模拟(Dr. Peter Tieleman)                                                  2014