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  • ISSN 1006-3080
  • CN 31-1691/TQ

基于分子对接研究小分子对冰核蛋白的微观抑制机理

胡响响 丁雅丽 冯玄 张然 石彤非 卫来

胡响响, 丁雅丽, 冯玄, 张然, 石彤非, 卫来. 基于分子对接研究小分子对冰核蛋白的微观抑制机理[J]. 华东理工大学学报(自然科学版). doi: 10.14135/j.cnki.1006-3080.20201218002
引用本文: 胡响响, 丁雅丽, 冯玄, 张然, 石彤非, 卫来. 基于分子对接研究小分子对冰核蛋白的微观抑制机理[J]. 华东理工大学学报(自然科学版). doi: 10.14135/j.cnki.1006-3080.20201218002
HU Xiangxiang, DING Yali, FENG Xuan, ZHANG Ran, SHI Tongfei, WEI Lai. Microscopic Inhibition Mechanism of Small Molecules on Ice Nucleation Protein Based on Molecular Docking[J]. Journal of East China University of Science and Technology. doi: 10.14135/j.cnki.1006-3080.20201218002
Citation: HU Xiangxiang, DING Yali, FENG Xuan, ZHANG Ran, SHI Tongfei, WEI Lai. Microscopic Inhibition Mechanism of Small Molecules on Ice Nucleation Protein Based on Molecular Docking[J]. Journal of East China University of Science and Technology. doi: 10.14135/j.cnki.1006-3080.20201218002

基于分子对接研究小分子对冰核蛋白的微观抑制机理

doi: 10.14135/j.cnki.1006-3080.20201218002
基金项目: 国家自然科学基金(21674114)
详细信息
    作者简介:

    胡响响(1996—),男,河南睢县人,硕士生,主要研究方向为高分子物理。E-mail:xxhu@ciac.ac.cn

    通讯作者:

    张 然,E-mail:rzhangciac@ciac.ac.cn

    石彤非,E-mail:tfshi@ciac.ac.cn

  • 中图分类号: O641

Microscopic Inhibition Mechanism of Small Molecules on Ice Nucleation Protein Based on Molecular Docking

  • 摘要: 自然界广泛存在着的冰核蛋白(INP)能够在微观尺度诱导水分子规整排列,提高冰点,而其蛋白三级结构仍未能通过实验确定。最新研究表明冰核蛋白具有与抗冻蛋白(AFP)结构相同的冰结合模板TXT,但INP模板面积更大导致其功能与AFP完全相反。相关研究表明INP可通过酪氨酸(TYR)阶梯结构二聚化形成新的β-螺旋二聚体进而增加结冰活性表面积来促进冰核的形成。同时在一系列对照实验中,发现聚甘油能够结合并抑制冰核细菌丁香假单胞菌INP的冰成核活性。因此,本文通过使用分子模拟软件AutoDock研究甘油和三聚甘油分子与北方假单胞菌的冰核蛋白模型之间的相互作用,以期阐释该抑制行为的分子机理以及是否在冰核蛋白类结构中具有普适性。结合信息显示了配体分子与TXT结冰模板和TYR阶梯结构之间的不同结合能力,并且在与TXT结冰模板的结合中发现有冰核蛋白其他残基参与结合。模拟结果表明配体分子与INP的特异性结合可能适用于其他具有类似结构的INP。该结果为聚甘油作为冷冻保护材料的开发和进一步理解冰核蛋白结冰机理提供了有用的理论信息。

     

  • 图  1  PbINP的三维模型

    Figure  1.  Three-dimension model of PbINP

    a-Cartoon model of PbINP; b-Tyrosine ladder side view; c-TXT freezing surface

    图  2  冰核蛋白模拟过程中产生的结构相对于初始结构的均方根偏差(RMSD),以及模拟结束时INP单体和二元体的空间结构视图(其中图(c)和(e)是图(b)和(d)中结构的俯视图)

    Figure  2.  Root mean square deviation (RMSD) of the structure produced during the simulation of ice nucleation protein with respect to the initial structure, and the views of the spatial structure of INP monomer and binary body at the end of simulation (in which Fig. (c) and (e) are the top views of the structures in Fig. (b) and (d)).

    图  3  配体分子与PbINP的结合模式

    Figure  3.  Binding modes of ligand molecule and PbINP

    表  1  配体分子与酪氨酸残基对接结果

    Table  1.   Result of ligand molecule docking TYR residues

    LigandResidue
    site
    Binding energy/
    (kcal·mol−1)
    ki/
    (μmol·L−1)
    Number of
    same clusters
    Glycerol18, 34, 50−3.81630157
    −4.87267.1523
    50, 66, 82−3.5272097
    −4.76323.2240
    98, 114, 130−4.13946.8583
    −4.81295.7152
    Triglycerol18, 34,5 0,
    66, 82
    −3.721870234
    66, 82, 98,
    114, 130
    −4.63404.52162
    下载: 导出CSV

    表  2  配体分子与苏氨酸残基对接结果

    Table  2.   Result of ligand molecule docking THR residues

    LigandResidue
    site
    Binding energy/
    (kcal·mol−1)
    ki/
    (μmol·L−1)
    Number of
    same clusters
    Glycerol5,7,21,23,37, 39−5.4798.41122
    −6.898.9372
    53,55,69,71,
    85 ,87
    −6.1829.32152
    101,103,117,
    119,133,135
    −6.4119.92186
    Triglycerol5,21,37,53−5.5782.22155
    7,23,39,55−3.821580187
    −5.37115.98108
    37,53,69,85−5.25142.24233
    39,55,71,87−4.8303.56292
    85,101,117,133−5.0217.51139
    87,103,119,135−6.839.78249
    下载: 导出CSV
  • [1] MAKI L R, GALYAN E L, CHANG−CHIEN M M. et al Ice nucleation induced by pseudomonas syringae[J]. Applied and Environmental Microbiology, 1974, 28(3): 456-459. doi: 10.1128/AM.28.3.456-459.1974
    [2] SCHMID D, PRIDMORE D, CAPITANI G, et al. Molecular organisation of the ice nucleation protein InaV from pseudomonas syringae[J]. Federation of European Biochemical Societies, Letters, 1997, 414(3): 590-594. doi: 10.1016/S0014-5793(97)01079-X
    [3] TSUMUKI H, KONNO H, MAEDA T, et al. An ice-nucleating active fungus isolated from the gut of the rice stem borer, Chilo suppressalis Walker (Lepidoptera: Pyralidae)[J]. Journal of Insect Physiology, 1992, 38(2): 119-121. doi: 10.1016/0022-1910(92)90040-K
    [4] 王恒生, 刁治民, 陈克龙, 等. 冰核微生物的研究动态及开发应用前景[J]. 江苏农业科学, 2014, 000(7): 17-21. doi: 10.3969/j.issn.1002-1302.2014.07.005
    [5] LINDOW S E, HIRANO S S, BARCHET W R, et al. Relationship between ice nucleation frequency of bacteria and frost injury[J]. Plant Physiology, 1982, 70(4): 1090−1093.
    [6] ARAI S, WATANABE M J. Freeze texturing of food materials by ice-nucleation with the bacterium Erwinia ananas[J]. Journal of the Agricultural Chemical Society of Japan, 1986, 50(1): 169-175.
    [7] 孙福在, 何礼远. 冰核活性细菌与植物霜冻的研究概况[J]. 植物保护, 1989, 015(004): 41-43.
    [8] GREEN R L, COROTTO L V, WARREN G J. Deletion mutagenesis of the ice nucleation gene from Pseudomonas syringae S203[J]. Molecular and General Genetics, 1988, 215(1): 165-172. doi: 10.1007/BF00331320
    [9] WOLBER P, WARREN G. Bacterialice-nucleation proteins[J]. Trends in Biochemical ences, 1989, 14(5): 179-182. doi: 10.1016/0968-0004(89)90270-3
    [10] 赵廷昌, 孙福在, 姜大志, 等. 冰核微生物中冰核基因重复序列PCR分析[J]. 微生物学通报, 2001(03): 40-45. doi: 10.3969/j.issn.0253-2654.2001.03.010
    [11] KAJAVA A V, LINDOW S E. A model of the three-dimensional structure of ice nucleation proteins[J]. Journal of Molecular Biology, 1993, 232(3): 709-717. doi: 10.1006/jmbi.1993.1424
    [12] GRAETHER S P, JIA Z C. Modeling pseudomonas syringae ice-nucleation protein as a β-helical protein[J]. Biophysical Journal, 2001, 80(3): 1169-1173. doi: 10.1016/S0006-3495(01)76093-6
    [13] GARNHAM C P, CAMPBELL R L, WALKER V. K, et al Novel dimeric β-helical model of an ice nucleation protein with bridged active sites[J]. BMC Structural Biology, 2011, 11(1): 36. doi: 10.1186/1472-6807-11-36
    [14] ZACHARIASSEN K E, KRISTIANSEN E. Ice nucleation and antinucleation in nature[J]. Cryobiology, 2000, 41(4): 257-279. doi: 10.1006/cryo.2000.2289
    [15] LEE M R, LEE R E, STRONG−GUNDERSON J M, et al. Isolation of ice-nucleating active bacteria from the freeze-tolerant frog, rana sylvatica[J]. Cryobiology, 1995, 32(4): 358-365. doi: 10.1006/cryo.1995.1036
    [16] KAWAHARA H, MASUDA K, OBATA H. Identification of a compound in chamaecyparis taiwanensis inhibiting the ice-nucleating activity of Pseudomonas fluorescens KUIN-1[J]. Bioence Biotechnology and Biochemistry, 2000, 64(12): 2651-2656. doi: 10.1271/bbb.64.2651
    [17] DOLEV M B, BRASLAVSKY I, DAVIES P L. Ice-binding proteins and their function[J]. Annual Review of Biochemistry, 2016, 85(1): 515-542. doi: 10.1146/annurev-biochem-060815-014546
    [18] KAWAHARA H, TAGAWA E, WATANABE C, et al. Characterization of anti-ice nucleation activity of the extract from coffee refuse[J]. Biocontrol Science, 2017, 22(4): 205-211. doi: 10.4265/bio.22.205
    [19] TAGAWA E, URA M, NAKATSUKA E, et al. Anti-ice nucleation activities of tyrosine peptide[J].Biocontrol Science, 2018, 23(2): 81−83.
    [20] WOWK B, FAHY G M. Inhibition of bacterial ice nucleation by polyglycerol polymers[J]. Cryobiology., 2002, 44(1): 14-23. doi: 10.1016/S0011-2240(02)00008-1
    [21] BABAYAN V K. Polyglycerols and polyglycerol esters in nutrition, health and disease[J]. Journal of Environmental Pathology, Toxicology and Oncology, 1986, 6(3−4): 15-24.
    [22] MICHAEL W R, COOTS R H. Metabolism of polyglycerol and polyglycerol esters[J]. Toxicology and Applied Pharmacology, 1971, 20(3): 334-345. doi: 10.1016/0041-008X(71)90277-8
    [23] WILSON R, VAN SCHIE B J, HOWES D. Overview of the preparation, use and biological studies on polyglycerol polyricinoleate (PGPR)[J]. Food and Chemical Toxicology, 1998, 36(9): 711-718.
    [24] 张艳芳. 甘油氧化反应热力学分析及炭载Pt基催化剂上动力学行为研究[D]. 上海: 华东理工大学, 2018.
    [25] MORRIS G. M, GOODSELL D S, HALLIDAY R. S, et al Automated docking using a lamarckian genetic algorithm and an empirical binding free energy function[J]. Journal of Computational Chemistry, 1998, 19(19): 1639-1662.
    [26] WETS J B, SOLIS F J. Minimization by random search techniques[J]. Mathematics of Operations Research, 1981, 6(1): 19-30. doi: 10.1287/moor.6.1.19
    [27] HUEY R, MORRIS G M, OLSON A J, et al. A semiempirical free energy force field with charge-based desolvation[J]. Journal of computational chemistry, 2007, 28(6): 1145-1152. doi: 10.1002/jcc.20634
    [28] AZIZAH R N, SUHARTI, YAHMIN. A molecular docking study of dehydroevodiamine as an inhibitor of epstein-barr virus protease[J]. IOP Conference Series: Materials ence and Engineering, 2020, 833(1): 012006.
    [29] FORLEMU N, WATKINS P, SLOOP J. Molecular docking of selective binding affinity of sulfonamide derivatives as potential antimalarial agents targeting the glycolytic enzymes: GAPDH, aldolase and TPI[J]. Open Journal of Biophysics, 2017, 7(1): 41-57. doi: 10.4236/ojbiphy.2017.71004
    [30] WATERHOUSE A, BERTONI M, BIENERT S, et al. SWISS-MODEL: Homology modelling of protein structures and complexes[J]. Nucleic Acids Research, 2018, 46(W1): W296−W303.
    [31] SPOEL D V D, LINDAHL E, HESS B, et al. GROMACS: Fast, flexible, and free[J]. Journal of Computational Chemistry, 2005, 26(16): 1701-1718. doi: 10.1002/jcc.20291
    [32] GUVENCH O, MALLAJOSYULA S S, RAMAN E P, et al. CHARMM additive all-atom force field for carbohydrate derivatives and its utility in polysaccharide and carbohydrate-protein modeling[J]. Journal of chemical theory and computation, 2011, 7(10): 3162-3180. doi: 10.1021/ct200328p
    [33] SCHRODINGER L L C. The PyMOL Molecular Graphics System, Version 2.4.0 Open-Source, Schrodinger, LLC, 2003−2020.
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出版历程
  • 收稿日期:  2020-12-18
  • 网络出版日期:  2021-02-07

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