The Prediction Of Conservative Neutral Epitope Of H5 Avian Influenza Virus And The Preliminary Design Of Anti-virus Polypeptide Using Protein Structure Modeling

The H5N1 avian influenza virus has widely spread in Asia, Europe and Africa, causing a large amount of economic loss. Moreover, the virus has infected human, resulting in lots of human died. With the spreading of the virus in birds, the human-by-human infection may become possible if the gene recombination and mutation occurs constantly. It is predicted that there will be more than 100 million human dead because of little or lack of immunity against the virus if the next pandemic breaks out by H5N1. WHO calls on each country to design the strategies for the prevention of the virus. Our research group have found three strains of broad neutral monoclonal antibodies, named 8H5, 8G9 and 10F7 respectively, all of which bind to various H5N1 virus strains well. These monoclonal antibodies are helpful in seeking the broad curative antibodies, developing the vaccine and designing the anti-virus drug against the high mutational H5N1 influenza virus.In this study, the structures of the three antibodies were modeled by the"canonical structure"method, and then the models were subjected to energy minimization in cvff force filed. A lot of verification test programs, such as energy analysis, Ramachandran plot and Profiles-3D were employed to make sure the structures were in good conformation.The three antibody models were subject to docking with three HA structures found in PDB (PDB ID: 1jsm, 2ibx and 2fk0). From the docking results, we analyzed the binding pattern between the antibodies and the HAs. The binding pattern between the individual antibody with the three HAs was used to search the broad neutral epitopes which the three antibodies binding to and the interacting polypeptides located in the antibodies which may be made use of the reference of the anti-virus drug.From the docking results analysis, we got the following conclusion: (1) The common epitopes of the three HAs against Fab8H5 were comprised as followings: (the residue in 1jsm) Asp⁶⁸, Asn⁷², (Glu¹¹², Lys¹¹³, Ile¹¹⁴), Pro¹¹⁸, Ser¹²⁰, Tyr¹³⁷, Tyr²⁵². (2) The common epitopes against Fab10F7 were: Asn⁷², (Glu¹¹², Lys¹¹³, Ile¹¹⁴), (Ser¹²⁰,Ser¹²¹), Arg¹⁴⁵, Tyr⁽164(,Tyr²⁵². (3) The epitopes against Fab8G9 located in the region Glu¹¹² to Ser¹²⁰. (4) The polypeptide located in Fab8H5 which was Tyr⁵⁰-Ser⁵¹-Ser⁵² -Asn⁽53(-Leu⁵⁴-Ala⁵⁵-Pro⁵⁶, the polypeptide located in Fab8G9 which was Gly⁹⁵-Ieu⁹⁶ -Ala⁹⁷-Thr⁹⁸-Leu⁹⁹-Met¹⁰⁰-Val^100a-Leu^100b-Pro^100c-Asp¹⁰¹-Tyr¹⁰², and the polypeptides located in Fab10F7 which were Ala²⁶-Tyr²⁷-Thr²⁸-Phe²⁹ -Thr³⁰-Ser³¹-Tyr³² and Gly⁹⁵-Gly⁹⁶-Thr⁹⁷-Gly⁹⁸-Asp⁹⁹-Phe¹⁰⁰-His^100a-Tyr⁽100b(-Ala^100c -Met^100d-Asp¹⁰¹-Tyr¹⁰² may be used as the references for the anti-virus drugs.The results will provide the valuable information to the development of the broad vaccine and to the design of the curative drug against H5 influenza virus, and the important reference for the research in the mechanic of virus infection and neutralization.