目前全世界有3千百万人感染艾滋病病毒。临床上较有效的抑制艾滋病病毒的药物是艾滋病病毒蛋白酶抑制剂药物（HIV PIs）如：Nelfinavir, Atazanavir等，艾滋病病毒蛋白酶是由艾滋病病毒编码并对其组装、成熟起关键作用的蛋白。艾滋病病毒蛋白酶的抑制剂药物能够抑制其活性从而抑制病毒成熟。但是这些药物本身会产生很多副作用，如高胆固醇、高血脂、心血管并发症、肝脏毒性等。这些副作用的产生可能是由于这些药物作用于人体细胞内其他功能蛋白分子，影响其功能所致，而该功能分子可能具有和艾滋病病毒蛋白酶相似的三维结构。本项目拟应用生物信息学、蛋白质X射线衍射晶体学、化学物学、细胞生物学等多手段找出艾滋病病毒抑制剂药物在人体内的作用蛋白，并解析其与抑制剂药物复合物的结构，优化并设计特异性更好的艾滋病病毒蛋白酶抑制剂药物，同时利用该药物作为工具研究其结合人体内的脱靶蛋白研究产生副作用的分子机制。

Now there are more than 30 million people infected with HIV. The effective drug to inhibit the virus is HIV protease inhibitor drugs (PIs),such as: Nelfinavir, Atazanavir and so on. HIV protease is coded by the HIV virus and it plays a key role on the assembling and maturity of the virus. The PIs can inhibit the activity of the virus to inhibit its maturity. But the drug will produce a lot of side effects, such as high cholesterol, high blood fat, cardiovascular complications and liver toxicity, etc. We infer that the side effects may be caused by the drug effect on other functional protein molecule in human cells, the function of the molecule is inhibited .The functional molecule may have the similar three dimensional structure to the HIV protease. So the goal of our research is to find the target protein of the PIs in human body, and analyze the structure of the complex , design specific better HIV protease inhibitor drugs, and at the same time, use the drug as a tool to study the molecular mechanism of side effects and produc the signal transduction pathways in vivo.