Abstract:

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 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.

Key words: HIV-1 protease, allosteric inhibitor, MM-PB/GBSA, CUDA, Amber, ff12SB force field