论文部分内容阅读
目的虚拟筛选基于结构的HIV-1整合酶抑制剂。方法从PDB(Protein Data Bank)下载HIV-1整合酶催化核心结构域与LEDGF/p75整合酶结合结构域(integrase binding domain,IBD)的晶体结构(PDB ID:2B4J),通过AutoDockTools对结构进行处理;从ZINC数据库下载化合物结构,用PyRx处理和转换成pdbqt格式,建立一个处理后的化合物数据库;以HIV整合酶为靶点,通过新的虚拟筛选工具PyRx运行AutoDock Vina,对ZINC数据库的化合物进行虚拟筛选;分析得到的小分子抑制剂与整合酶之间的结合情况,并用PyMol对小分子抑制剂与整合酶的结合模式进行3D建模。结果经3轮筛选,发现5个高活性的HIV-1整合酶抑制剂ZINC9486894、ZINC47636331、ZINC57383520、ZINC68964708、ZINC73549421;5个小分子抑制剂与整合酶之间的结合主要是氢键结合力和疏水相互作用。结论通过PyRx运行AutoDock Vina,从ZINC数据库的化合物中筛选出5个新的HIV-1整合酶抑制剂。
Purpose To screen structurally based HIV-1 integrase inhibitors. Methods The crystal structure (PDB ID: 2B4J) of HIV-1 integrase catalytic core domain and LEDGF / p75 integrase binding domain (IBD) was downloaded from PDB (Protein Data Bank) and the structure was processed by AutoDockTools ; Compound structure was downloaded from the ZINC database, processed with PyRx and converted to pdbqt format to create a database of processed compounds; AutoDock Vina was run with the help of PyRx, a new virtual screening tool targeting HIV integrase, to the ZINC database Virtual screening; analyze the binding between the small molecule inhibitor and the integrase obtained, and model the binding mode of the small molecule inhibitor and integrase with PyMol. Results After three rounds of screening, five highly active HIV-1 integrase inhibitors, ZINC9486894, ZINC47636331, ZINC57383520, ZINC68964708 and ZINC73549421, were found. The binding between the five small molecule inhibitors and integrase was mainly hydrogen bonding and hydrophobic interaction. Conclusions Five novel HIV-1 integrase inhibitors were screened from compounds in the ZINC database using AutoDock Vina with PyRx.