| Since their reemergence in 2003, highly pathogenic avian influenza A (H5N1) 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 (H5N1) 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 H5N1 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.Amino acid sequences of HA from subtype H3 and H5 downloaded from influenza database of NCBI were divided into six sets of Set1, 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 al. We constructed 3D structures of dominance sequence models according to the crystal structure 1MQM and 1JSN as templates and determined the receptor binding domains with 6.5? from ligand based on Modeller9 V2 module in DS 2.0(Discovery Studio 2.0). The result shows that receptor binding domains were constituted by 24 amino acids in H3 such as 98, 133, 134, and 91, 129, 130 etc. 27 amino acids in H5.The conservation amino acids of receptor binding site 98, 134, 136, 153, 154, 184 from H3 and 149, 180, 191 from H5 indicated that such sites were not important during virus recognize and bind receptors. The results of entropy value of human H3 strain and avian strain are significant different on receptor binding site 133, 135, 137, 138, 145, 155, 186, 190, 222, 225, 226 and 227, while the results of human H5 strain and avian strain are significant different on receptor binding site 129, 141, 183 and 218, so these differences may determine the host specificity. It is interesting that H3 and H5 have different receptor binding specificity. Docking the sialic acid molecule into receptor binding domains on 3D structure of HA by DS 2.0 Zdock module followed by optimizing the structure to use Rdock module, then dynamic simulation of the compounds. We definited promoting banding amino acid and repressing banding amino acid with there different banding energy on receptor binding site. For instance, Lys, Arg, Ser, Asn, Ala, Gln, Ile, Thr and Tyr promoted the binding for their conspicuous lower binding energy, while Glu on site 186 obviously adverse to stability.One or more key amino acid belong to site in 131, 149, 181, 182, 186, 190, 221 and 224 transformed to promoting amino acid on receptor binding sites of H5, such as Lys, Arg, Ser, Asn, Ala, Gln, Ile, Thr and Tyr, is the most important factor for human infected with avian influenza virus. When these sites changed to Tyr, Arg, Asn, Lys, Ser and Gln which in low binding energy or forming hydrogen bond easily, binding energy and the number of hydrogen bond withα-2,6 sialic acid molecule may be promoted significantly just by single site of HA changed. H5N1 avian influenza virus may enhance there ability to infect human by these changing.
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