We performed 100 nanosecond molecular dynamics simulation for the allosteric inhibitor system and active site inhibitor system of HIV-1 protease on NVIDIA CUDA GPU with new developed force field ffl2SB. We also calculated the bind free energy of inhibitor TL-3 and HIV-1 protease with MM-PB/GBSA. Exo site binded fragment 2-methylcyclohexanol is favorable for the binding of inhibitor near the site. The bind free energy of inhibitor TL-3 and protease is -85.78 kcal/mol in allosteric inhibitor system and -79. 45 kcal/mol in active site inhibitor system. These results are benefit for the deep learning of the dynamics process of HIV-1 PR, which provides important guidelines for the design of new strong inhibitors.%采用新开发的ff12SB力场在NVIDIA CUDA GPU上对HIV-1蛋白酶的活性位抑制剂体系和异位抑制剂体系分别进行了100 ns的长时间分子动力学模拟,并用MM-PB/GBSA方法计算了活性位点抑制剂TL-3与HIV-1蛋白酶的结合自由能.异位抑制剂体系中分子片段2-甲基环己醇结合在Exo位,有利于抑制剂被束缚在活性位点附近.异位抑制剂体系中抑制剂TL-3与蛋白酶的结合自由能为-85.78 kcal/mol,活性位抑制剂体系中为-79.45 kcal/mol.这些结果有助于深入了解HIV-1 PR的动力学过程,为设计新型强效抑制剂提供了新见解.
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