HIV-1蛋白酶异位抑制剂体系的长时间分子动力学模拟  

Long-time molecular dynamics simulation of allosteric inhibitor system of HIV-1 protease

作　　者：王加磊[1] 孟现美[1] 张庆刚[1] 张怿慈[1] 张少龙[1] 

机构地区：[1]山东师范大学物理与电子科学学院,山东济南250014

出　　处：《山东科学》2013年第2期1-6,共6页Shandong Science

基　　金：国家自然科学基金(11274206);山东省自然科学基金(ZR2011HM048);高等学校博士学科点专项科研基金(20093704110001)

摘　　要：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。We performed t00 nanosecond molecular dynamics simulation for the allosteric inhibitor system and active site inhibitor system of HIV-1 protease on NVlDIA CUDA GPU with new developed force field ff12SB. 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.

关 键 词：HIV-I蛋白酶 异位抑制剂 MM-PB/GBSA CUDA AMBER ff12SB力场 

分 类 号：O641.12[理学—物理化学]