Prediction of a common neutralizing epitope of H5N1 avian influenza virus by in silico molecular docking

作     者：YAN YuanQing LI ShaoWei YANG ChunYan LUO WenXin WANG MingQiao CHEN YiXin LUO HaiFeng wu Ting ZHANG Jun XIA NingShao 

作者机构：National Institute of Diagnostics and Vaccine Development in Infectious Diseases/Key Laboratory of the Ministry of Education forCell Biology and Tumor Cell Engineering Xiamen University Xiamen 361005 China 

出 版 物：《Chinese Science Bulletin》 (Chin. Sci. Bull.)

年 卷 期：2008年第53卷第6期

页      面：868-877页

核心收录：

学科分类：090603[农学-临床兽医学] 09[农学] 0906[农学-兽医学] 

基　　金：the National Natural Science Foundation of China (Grant Nos. 30500092, 30640017 and 30600106) National Science and Technology Project in the 10th Five-Year Period (Grant No. 2004BA519A73) Key Projects in the National Science & Technology Pillar Program (Grant No. 2006BAI01B06) Major Science and Technology Project of Fujian Province (Grant No. 2004YZ01) Key Science and Technology Project of Fujian Province (Grant No. 2005Y020) 

主　　题：禽流感 H5N1病毒 抗原决定基 红血球凝聚素 

摘      要：The H5N1 avian influenza virus (AIV) has widely spread in Asia, Europe and Africa, making a large amount of economic loss. Recently, our research group has screened a common neutralizing mono- clonal antibody named 8H5, which can neutralize almost all H5 subtype AIV ever isolated so far. Obvi- ously, this monoclonal antibody would benefit for research and development of the universal AIV vac- cine and design of the drug against H5N1 AIV in high mutation rate. In this study, the homology mod- eling was applied to generate the 3D structure of 8H5 Fab fragment, and canonical structure method was used to define the specified loop conformation of CDR regions. The model was subjected to en- ergy minimization in cvff force field with Discovery module in Insight II program. The resulting model has correct stereochemistry as gauged from the Ramachandran plot calculation and good 3D-structure compatibility as assessed by interaction energy analysis, solvent accessible surface (SAS) analysis, and Profiles-3D approach. Furthermore, the 8H5 Fab model was subjected to docking with three H5 subtype hemagglutinin (HA) structures deposited in PDB (ID No: 1jsm, 2ibx and 2fk0) respectively. The result indicates that the three docked complexes share a common binding interface, but differ in bind- ing angle related with HA structure similarity between viral subtypes. In the light of the three HA inter- faces with structural homology analysis, the common neutralizing epitope on HA recognized by 8H5 consists of 9 incontinuous amino acid residues: Asp68, Asn72, Glu112, Lys113, Ile114, Pro118, Ser120, Tyr137, Tyr252 (numbered as for 1jsm sequence). The primary purpose of the present work is to provide some insight into structure and binding details of a common neutralizing epitope of H5N1 AIV, thereby aiding in the structure-based design of universal AIV vaccines and anti-virus therapeutic drugs.