氮杂茋衍生物靶向虚拟筛选研究

Research on targeted virtual screening of aza stilbene derivatives

为寻求新的具有强生理活性的茋类化合物,设计了237个全新结构的氮杂茋小分子.基于靶标虚拟筛选平台TarFisDock,针对病毒类靶标作广泛筛选,所设计化合物均集中结合于HIV蛋白酶的活性位点,这一结果已经为HIV蛋白酶正向对接所证实.通过统计所设计分子的体积、脂水分配系数、小分子-蛋白间氢键,归纳出分子的理化性质与对接结果中结合能量的关系,并考察了分子结构对能量得分的影响.筛选结果提示HIV蛋白酶可能是氮杂茋衍生物抑制HIV的高活性靶标.

To seek new stilbene analogs with high activity,237 aza stilbene derivatives with whole new structures are designed. During screening targets of viral infection supported by the target-based virtual screening service of TarFisDock,most of the designed molecules can act with the active site of HIV protease. The reliability of the result is also confirmed by docking HIV protease and 237 molecules. The effects of some physicochemical properties on the docking energy score,such as molecular volume,octanol/water partition coefficient,hydrogen bond formed between small molecules and protein are explored. And molecular structure factors affecting docking results are also discussed. Screening results suggest that HIV protease may be the highly-active target of aza stilbene derivatives to inhibit HIV.