HIV-1整合酶二聚体与硫氮硫扎平抑制剂相互作用.pdfVIP

HIV-1 整合酶二聚体与硫氮硫扎平抑制剂相互作用 ， ， 1 2 2 王丽东 * ，王存新 (1 重庆工商大学药物化学与化学生物学研究中心，重庆，400067 ； 2 北京工业大学生命科学与生物工程学院，北京 100022) 摘要：目的 研究HIV-1 整合酶 (IN) 与已知抑制剂硫氮硫扎平类的结合模式、结合强度， 为寻找具有更好活性的抗HIV 药物提供帮助。方法 用同源模建方法搭建每条单链核心区具 有两个Mg2+ 的IN 二聚体模型。分子对接搜索能量较低的硫氮硫扎平类化合物-IN 对接复合 物，并对复合物进行了分子动力学模拟。结果 得到了每条单链核心区具有两个 Mg2+ 的 IN 二聚体模型。得到了能量较低的多个硫氮硫扎平类化合物-IN 对接复合物。发现这些构象具 有很强的相似性，硫氮硫扎平类化合物具有很强的结合专一性。对于构象的研究发现，氮硫 扎平类化合物与 IN 活性位点的一些氨基酸有极重要的相互作用。结论 建立的模型能够有 效地反映HIV-1 IN 与硫氮硫扎平类抑制剂的作用特点和作用模式。为进一步的分子改造、 分子设计提供分子水平的帮助。 关键词：分子模拟； HIV-1 整合酶；硫氮硫扎平类抑制剂; 金属离子 Study on the interaction between HIV-1 integrase dimer and thiazolothiazepines inhibitors WANG Li-dong (Research Center of Pharmaceutical Chemistry Chemobiology, Chongqing Technology and Business University, Chongqing, 400067, China) ABSTRACT: OBJECTIVE Study the binding sites and binding modes of HIV-1 integrase and its inhibitors- thiazolothiazepines. These studies will be helpful for design and discovery of new active anti-AIDS drugs. METHODS To model HIV-1 IN dimer which has two Mg2+ icons in each catalytic core domain, homology modeling method was adopted. To search low energy thiazolothiazepines-IN complex, molecular docking was used. Furthermore, the molecular docking and molecular dynamics simulation were used to study the binding sites and binding modes of thiazolothiazepines-IN complex. RESULTS HIV-1 IN dimer which has two Mg2+ icons in each catalytic core domain was gained. Several thiazolothiazepines-IN complexes with low energy were found. From the docking results, it is found that these complexes were very similar in spacial configurations. Moreover, the docking results show that the thiazolothiazepines have highly bonding specialty and they have many significant biological contacts or interactions with amino acids of HI