乙型肝炎表面抗原片段三维结构的同源模建及其配体的设计

Homology Modeling of Three-dimension Structure of Hepatitis B Surface Antigen Fragment and Its Ligand Design

利用同源模建和分子动力学优化得到了一种乙肝表面抗原片段的三维结构 .通过对活性部位的分析 ,设计了与抗原片段相结合的配体 .讨论了 Trp1 63 ,Trp1 65和 Pro70对于紧密结合配体所起的重要作用 ,抗原片段与配体之间的氢键也决定了它们结合的相对位置 .从复合物得到的结构信息将有助于揭示配体与乙肝抗原的作用机理 。

By means of the homology modeling and docking methods, a theoretical study on hepatitis B surface antigen(HBsAg) fragment(44_170) was performed. The three-dimension structure of HBsAg fragment(44_170) is built up based on the crystal structures of whey acidic protein(PDB code 1CJH) and ricin glycosidase (PDB code 2AAI). A new ligand is designed based on the structure of acceptor HBsAg(44_170) and the ligand is docking to HBsAg fragment. The result shows that Trp163 and Trp165 in the complex have strong van der Waals contacts with the ligand, and this result is in agreement with the experimental one in refrence reported by Wang et al. The hydrogen bonding interactions between ligand and tryptophan residues as well as proline residue of HBsAg also play an important role in locating effects. The results obtained may be helpful for further studies of the structure-based ligand designing of new compounds.