中文摘要：

以原型泡沫病毒（PFV）整合酶（Integrase，IN）-雷特格韦（Rahegravir，RLV）复合物晶体结构为模板．同源模建了HIV-1IN-RIⅣ复合物模型。恰当的Ramachandranplot分布和Profile-3D数值结果验证了复合物模型的合理性。用分子动力学（Moleeulardynamics，MD）模拟优化了模建复合物，分子整体结构发生微幅调整．其中活性口袋区关键残基D116-Mgl-Mg2-E152有一定关联柔性摆动。这对于IN结合柔性较大的RLV分子较为有利。运动性分析表明．RLV分子围绕中心羟基嘧啶．两侧恶二唑和氟苯略微靠近．通过与晶体结构及对接结果对比发现．D116和N155可能是识别RLV抑制剂最为关键的两个残基．

英文摘要：

Based on the template of prototype foamy virus （PFV） integrase （IN）-raltegravir （RLV） complex crystal structure, the homology model of HIV-1 IN-RLV was developed. Both appropriate Ramachandran plot distribution and Profile-3D values verified the rationality of the homology complex model. After optimization by molecular dynamics （MD） simulation,the whole molecule structure of the modeled complex exhibited slight adjustment. The key residues in active pocket （i.e.,Dl16-Mgl- Mg2-E152） flexibly and correlatively swung to some extent, which may be beneficial for HIV-1 IN associating with highly flexible RLV molecule. Motion analysis showed that both sides of oxadiazole group and fluorobenzene group of RLV molecule slightly move close to each other around the methylpyrimidin group. Compared with the previous crystal structure and docking results,it was found that D116 and N155 may be the most important key residues for the recognition of RLV inhibitor. The results generated from the above simulation should be theoretically useful for the further drug design based on the structure of HIV-1 IN.