H5亚型流感病毒凝素与宿主范围局限性相关功能区识别与分析-预防兽医学专业毕业论文.docx

Thr、Tyr等促结合氨基酸突变时；尤其是这些位点突变为Tyr、Arg、Asn、Lys、 Thr、Tyr等促结合氨基酸突变时；尤其是这些位点突变为Tyr、Arg、Asn、Lys、 Ser、Gin等低结合能或易形成氢键的氨基酸时，血凝素仅单个位点变化就可显著 提高与a．2，6唾液酸分子的结合能和氢键数量。推测这些变化可使H5N1亚型禽流感 病毒对人类感染能力提高。 关键词：禽流感病毒；H5N1：受体结合位点；同源建模；动力学模拟；分子对接 Identification Identification and Analysis of Host-range Restriction Related Function Domains on Hemagglutinin of H5 Influenza Viruses ^bstract Since their reemergence in 2003，highly pathogenic avian influenza A(HSNI) viruses have reached epidemic levels among poultry in world and have caused a still increasing number of more than 378 reported human infections and 238 deaths．They have posed great threatens not only to birds，but also to humans．Although the increasing of the human cases，the faculty of the virus transmitting among parsons is still very limited．However,the accumulated number of human cases means that the human pandemic caused by avian influenza A(H5N I)virus is impending．The mechanism on how the viruses break the species barriers to infect human beings is still not clear and the agreement on what changes Can lead to the binding affinity of the viruses converting from poultry to humans is not reached yet．Therefore，identifying the differences on the receptor binding domains of H5N 1 influenza viruses between human and poultry strains on both sequence and structure levels are the key step toward fully understand of their species a crossing mechanism． Amlno acid sequences of HA from subtype H3 and H5 downloaded from influenza database of NCBl were divided into six sets of Setl，Set2，Set3，Set4，Set5 and Set6 according to their subtype and host origins．ClustalX 1．83 and Entropy 2．5 were used to construct dominance sequence module for each set by multiple sequence alignment，entropy calculation，and cluster analysis et a1．We constructed 3D structures of dominance sequence models according to the crystal structure 1 MQM and 1 JSN as templates and determined the receptor binding domains with 6．5A from ligand based on Modeller9 V2 module in DS 2