伏马菌素B_1特异单链抗体的同源建模及分子对接模拟研究
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摘要
目的分析伏马菌素B1(Fumonisin B1,FB1)与其特异单链抗体的分子互作模式。方法通过同源建模构建和优化抗FB1单链抗体的三维结构,结合Procheck和Verify 3D等方法评价得到稳定的抗体模型,利用分子对接研究单链抗体与其抗原FB1的结合特性、疏水性和表面静电力作用。结果单链抗体的互补决定区参与同其抗原FB1的结合,抗体与抗原之间不仅形成稳定的氢键,疏水性和静电力的匹配也很好。结论氢键结合力、分子间疏水相互作用和静电力的共同作用,使得单链抗体形成一个能够与FB1高度互补的相互作用区域,并在抗体与抗原的特异性识别及结合稳定性等方面起着关键作用。
To reveal the molecular interaction model between fumonisin B1(FB1) and its specific single chain variable fragment(scFv) antibody, the three dimensional structure of an anti-FB1 scFv antibody was modeled and refined using homology modeling for molecular docking analysis. Procheck and Verify 3D methods were used to confirm the reliability of the scFv conformation. The recognition and interaction including hydrogen bonding,hydrophobic and electrostatic properties between the scFv antibody and FB1 were analyzed by molecular docking method. The results showed that the complementarity-determining regions(CDRs) of the scFv antibody directly face FB1 molecule in the antibody-antigen complex. The hydrogen bonds are steadily formed between the scFv and its antigen; also the hydrophobic interaction and electrostatic matching of the scFv antibody are in good complementary with FB1 molecule. In conclusion, the effects of hydrogen bonding, electrostatic and hydrophobic interaction together make the scFv antibody forming a favorable binding pocket that is highly complementary to FB1, and this unique feature plays a vital role in the specific recognition and binding stability of antibody-antigen complex.
To reveal the molecular interaction model between fumonisin B1(FB1) and its specific single chain variable fragment(scFv) antibody, the three dimensional structure of an anti-FB1 scFv antibody was modeled and refined using homology modeling for molecular docking analysis. Procheck and Verify 3D methods were used to confirm the reliability of the scFv conformation. The recognition and interaction including hydrogen bonding,hydrophobic and electrostatic properties between the scFv antibody and FB1 were analyzed by molecular docking method. The results showed that the complementarity-determining regions(CDRs) of the scFv antibody directly face FB1 molecule in the antibody-antigen complex. The hydrogen bonds are steadily formed between the scFv and its antigen; also the hydrophobic interaction and electrostatic matching of the scFv antibody are in good complementary with FB1 molecule. In conclusion, the effects of hydrogen bonding, electrostatic and hydrophobic interaction together make the scFv antibody forming a favorable binding pocket that is highly complementary to FB1, and this unique feature plays a vital role in the specific recognition and binding stability of antibody-antigen complex.
引文
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[3]Wang JH,Zhang JB,Li HP,et al.Pathogenicity of Fusarium temperatum isolated from maize in China[J].J Phytopath,2014,162:147-157.
[4]Han Z,Ren Y,Liu X,et al.A reliable isotope dilution method for simultaneous determination of fumonisins B1,B2and B3in traditional Chinese medicines by ultra-highperformance liquid chromatography-tandem mass spectrometry[J].J Sep Sci,2010,33(17/18):2723-2733.
[5]Katerere DR,Stockenstrm S,Thembo KM,et al.A preliminary survey of mycological and fumonisin and aflatoxin contamination of African traditional herbal medicines sold in South Africa[J].Hum Exp Toxicol,2008,27(11):793-798.
[6]Omurtag GZ,Yazicio lu D.Determination of fumonisins B1and B2in herbal tea and medicinal plants in Turkey by high-performance liquid chromatography[J].J Food Prot,2004,67(8):1782-1786.
[7]Myburg RB,Dutton MF,Chuturgoon AA.Cytotoxicity of fumonisin B1,diethylnitrosamine,and catechol on the SNO esophageal cancer cell line[J].Environ Health Persp,2002,110(8):813-815.
[8]Rheeder JP,Marasas WF,Thiel PG,et al.Fusarium moniliforme and fumonisins in corn in relation to human esophageal cancer in Transkei[J].Phytopathology,1992,82(3):353-357.
[9]Sun G,Wang S,Hu X,et al.Fumonisin B1contamination of home-grown corn in high-risk areas for esophageal and liver cancer in China[J].Food Addit Contam,2007,24(2):181-185.
[10]Ueno Y,Iijima K,Wang SD,et al.Fumonisins as a possible contributory risk factor for primary liver cancer:A 3-year study of corn harvested in Haimen[J].Food Chem Toxicol,1997,35(12):1143-1150.
[11]Scott PM.Recent research on fumonisins:a review[J].Food Addit Contam Part A Chem Anal Control Expo Risk Assess,2012,29(2):242-248.
[12]Devarajan S,Sharmila JS.Computational studies of beta amyloid(β)with p75NTR receptor:a novel therapeutic target in Alzheimer's disease[J].Adv Bioinformatics,2014,2014:736378.
[13]Li X,Li P,Zhang Q,et al.Molecular characterization of monoclonal antibodies against aflatoxins:a possible explanation for the highest sensitivity[J].Anal Chem,2012,84(12):5229-5235.
[14]Lassila JK,Privett HK,Allen BD,et al.Combinatorial methods for small-molecule placement in computational enzyme design[J].Proc Natl Acad Sci USA,2006,103(45):16710-16715.
[15]Pérez S,Tvaroska I.Carbohydrate-protein interactions:molecular modeling insights[J].Adv Carbohydr Chem Biochem,2014,71:9-136.
[16]Azcona Olivera JI,Abouzied MM,Plattner RD,et al.Generation of antibodies reactive with fumonisins B1,B2,and B3by using cholera toxin as the carrier-adjuvant[J].Appl Environ Microbiol,1992,58(1):169-173.
[17]Liu JL,Hu ZQ,Xing S,et al.Attainment of 15-fold higher affinity of a Fusarium-specific single-chain antibody by directed molecular evolution coupled to phage display[J].Mol Biotechnol,2012,52(2):111-122.
[18]Fukuda I,Kojoh K,Tabata N,et al.In vitro evolution of single-chain antibodies using m RNA display[J].Nucleic Acids Res,2006,34(19):e127.