中文摘要：

用分子动力学（MD）模拟方法优化了HIV-1病毒DNA与整合酶（IN）二聚体（IN2）复合物模型结构,并分析了HIV-1病毒DNA结合IN2后的构象变化.结果表明,按照HIV-1病毒DNA与IN2结合能力的强度,病毒DNA可分为五个区域：非结合区、强结合区1、弱结合区、强结合区2和反应区,并用结合自由能计算验证了该分区的合理性.与未结合IN2的病毒DNA相比,复合物模型中病毒DNA除了非结合区碱基外,其它四个区域的碱基构象变化较大.复合物模型中病毒DNA主链较大程度地偏离标准B型DNA以及结合部位的小沟变宽都是识别IN的结构基础.模拟结果与实验数据吻合较好,为基于HIV-1 IN的药物分子设计提供了一定的结构信息.

英文摘要：

The complex model structure of human immunodeficiency virus-1 （HIV-1） DNA with integrase （IN） dimer （IN2） was refined through molecular dynamics （MD） simulation, and the viral DNA conformational change was explored after binding with IN2. The result showed that the viral DNA could be divided into five regions （i.e. non-binding region, high-affinity region 1, weak-affinity region, high-affinity region 2, and reaction region） according to the binding power with IN2. The partition rationality for viral DNA was confirmed through binding free energy computation. Compared with the viral DNA before binding with IN2, some big conformational changes occurred for the bases in the four binding regions other than the non-binding region for the viral DNA complexed with INz. The obvious deviation from standard B-DNA in the viral DNA main chain of the complex and the broading of the minor groove in the binding site were both the structural basis for the recognition of viral DNA with IN. The simulation results basically agreed with experimental data, which provided some structural information for the drug design based on the structure of HIV-1 IN.