HIV-1蛋白酶产物释放过程的分子动力学模拟研究

We used tha all-atom simulation method to study the product releasing process when the substrate was cleaved. We increased the temperature of products to 500K~550K to enhance their fluctuations, to accelerate the releasing process. We have observed two product releasing mode in the simulation results. In the product releasing mode I, the products lateral move away from the binding prokect, in which the fluctuations by high temperature play an important role. This releasing mode is similar to the coarse-grianed simulation results of product releasing and the all-atom simulation results of inhibitors escaping from the binding pokect in previous studies. In the product releasing mode II, one of the products inserts into the binding pokect, while the other one was pushed out by the inserted one. The releasing process of mode II was similar to the simulation results of single wall carbon nanotube self-assemble and spontaneous insertion of DNA into carbon nanotubes. The driving forces were the VDW and electrostatic interaction between the protease and the inserted product in mode II. During the product releasing process, the flaps of protease were in the closed configuration, indicating that the product releasing process does not need the opening of the flaps. This study gives a atomistic picture of the product releasing process of HIV-1 protease system.