抗DON单域重链抗体序列分析及三维建模与对接

Sequence analysis,3-D modeling and molecular docking of anti-deoxynivalenol single-domain heavy chain antibody

探讨应用分子模拟与对接技术预测抗脱氧雪腐镰刀菌烯醇(DON)单域重链抗体(DONIV2)的三维结构及其与DON的结合模式。采用生物信息学相关工具和网站分析预测DONIV2的理化特性及其二级结构,同源建模方法获得三级结构,然后采用分子对接软件Autodock 4.2将三维结构模型与DON进行分子对接。二级结构和三级结构分析显示,DONIV2由10个β片层结构组成,CDR区为无规则卷曲结构,位于分子的一端,在CDR1、CDR2与CDR3之间形成1条宽度约为1.2 nm的凹槽结构。对接结果显示,可能的DON结合位点由Arg59、Arg103和Arg105等残基组成,他们位于CDR2和CDR3区域。表明通过分子模拟与对接相关工具获得了DONIV2的一、二、三级结构及可能的结合活性位点,为深入认识DON与抗体相互作用机理提供了理论指导,并为下一步DONIV2体外亲和力的成熟提供了线索。

This study amied to predict the 3-D structure and binding mode of anti-deoxynivalenol（DON）single-domain heavy chain antibody（named DONIV2）.The molecular modeling and docking technology were employed by utilizing relative bioinformatics tools and on-line resources.The 3-D structure of DONIV2 was generated by SWISS-MODEL homologous modeling,and then docked with deoxynivalenol（DON） using AutoDock 4.2.The modeling data showed that DONIV2 had 10 β sheet structure and the second structure of CDRs was coil.All the three CDRs were located on the one side of the molecule and made up of a 4 nm×3 nm antibody-antigen（Ab-Ag） interface.A groove with width about 1.2 nm was formed between the CDR1（or CDR2） and CDR3.The probable binding sites were Arg59,Arg103 and Arg105,which were located on the CDR2 and CDR3.Interestingly,arginine other than tyrosine was one of the largest contributors to Ab-Ag interface composition at 20.7%.These data help to understand the mechanism of interaction between DON and DONIV2.Furthermore,it provides guidance for in vitro affinity maturation of DONIV2.