Prediction of a common neutralizing epitope of H5N1 avian influenza virus by in silico molecular docking
Prediction of a common neutralizing epitope of H5N1 avian influenza virus by in silico molecular docking
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DOI：
10.1007/s11434-008-0161-4
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发表时间：
2008-03
影响因子：
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通讯作者：
Yuan-qing Yan;Shaowei Li;Chunyan Yang;Wen-xin Luo;Ming-qiao Wang;Yixin Chen;Haifeng Luo;Ting Wu;Jun Zhang;N. Xia
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文献类型：
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作者：
Yuan-qing Yan;Shaowei Li;Chunyan Yang;Wen-xin Luo;Ming-qiao Wang;Yixin Chen;Haifeng Luo;Ting Wu;Jun Zhang;N. Xia
H5 N1禽流感病毒（AIV）在亚洲、欧洲和非洲等地广泛传播，造成了巨大的经济损失。最近，本课题组筛选出一株通用的中和性单克隆抗体，命名为8H 5，它能中和迄今为止分离到的几乎所有H5亚型AIV。该单克隆抗体为研制通用型禽流感疫苗和设计抗高突变H5 N1禽流感病毒的药物奠定了基础。本研究采用同源模建方法构建了8H 5 Fab片段的三维结构，并采用“规范结构”方法确定了CDR区的特定环状构象。在Insight II程序的Discovery模块中，对模型进行了cvff力场下的能量最小化处理。根据Ramachandran图计算，所得模型具有正确的立体化学，并且通过相互作用能分析、溶剂可及表面（SAS）分析和Profiles-3D方法评估，具有良好的3D结构兼容性。此外，将8H 5 Fab模型分别与PDB中保藏的三种H5亚型血凝素（HA）结构（ID No：1 jsm、2 ibx和2fk 0）进行对接。结果表明，三种对接的复合物具有共同的结合界面，但结合角度不同，这与病毒亚型之间HA结构的相似性有关。根据3个HA界面的结构同源性分析，8H 5识别的HA上的共同中和表位由9个不连续的氨基酸残基组成：Asp 68，Asn 72，Glu 112，Lys 113，Ile 114，Pro 118，Ser 120，Tyr 137，Tyr 252（编号与1 jsm序列相同）。
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 monoclonal antibody named 8H5, which can neutralize almost all H5 subtype AIV ever isolated so far. Obviously, this monoclonal antibody would benefit for research and development of the universal AIV vaccine and design of the drug against H5N1 AIV in high mutation rate. In this study, the homology modeling 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 energy 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 binding angle related with HA structure similarity between viral subtypes. In the light of the three HA interfaces 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).