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H5N1禽流感病毒已经在亚洲、欧洲和非洲广泛传播,造成了巨大损失.最近我们鉴定出一株对多种来源的H5N1代表株均有良好中和活性的、识别H5亚型血凝素(hemagglutinin,HA)的广谱单克隆抗体8H5,它对寻找克服禽流感高变性的广谱治疗性抗体、疫苗和药物具有重要价值.本研究应用分子模拟技术,采用“典范结构”方法对8H5抗体Fab片段进行结构模建,并通过能量分析、SAS值分析、“拉曼强传图”检验、profile-3D分析等理论验证,获得较为合理的8H5Fab的三维空间结构.8H5Fab与3种HA蛋白晶体结构的分子对接结果表明,8H5抗体与HA蛋白的作用模式与HA宿主来源无关,但与HA结构的亚型相似性相关.综合抗原同源比对结果,推测8H5抗体识别的广谱中和表位是由HA上的Asp68,Asn72,Glu112,Lys113,Ile114,Pro118,Ser120,Tyr137,Tyr252不连续氨基酸残基组成的构象表位.这一模型将为H5亚型禽流感病毒广谱疫苗和治疗性药物的分子设计提供依据。
H5N1 bird flu virus has spread widely in Asia, Europe and Africa, causing great losses.We recently identified a H5N1 representative strains of various sources have good neutralizing activity of the H5 subtype hemagglutinin (hemagglutinin , HA) broad-spectrum monoclonal antibody 8H5, which is of great value in finding broad-spectrum therapeutic antibodies, vaccines and drugs for overcoming the high degeneration of bird flu.In this study, molecular modeling technique was used to study the effect of 8H5 Fab fragment of antibody was modeled and the reasonable 3D structure of 8H5Fab was obtained by energy analysis, SAS value analysis, Raman strong transfer test and profile-3D analysis, The molecular docking results of the HA protein crystal structure show that the mode of action of the 8H5 antibody and the HA protein has nothing to do with the HA host source but is related to the subtype similarity of the HA structure.It is speculated that the broad spectrum of the 8H5 antibody recognition The neutralizing epitope is a conformational epitope consisting of discontinuous amino acid residues Asp68, Asn72, Glu112, Lys113, Ile114, Pro118, Ser120, Tyr137, Tyr252 on HA This model will provide a broad spectrum of H5 subtype avian influenza virus Vaccine and Therapeutic drug molecules designed to provide the basis.