关键词: MM-PBSA, 结合自由能, HIV-1蛋白酶, 分子片段, 异位抑制剂

Abstract:

We performed 8 ns of molecular dynamics simulation for the allosteric inhibitor and active site inhibitor system of HIV-1 protease. We also calculated their binding free energy with MM-PBSA. The free energy of inhibitor binding to protease is -90.30 kcal/mol in allosteric inhibitor system and the energy is -59.58 kcal/mol in active site inhibitor system. Molecular fragment 4DX stuck at protease exo site reduces the scope of residue activities near the active site in allosteric inhibitor system. It has favorable effect on the binding of inhibitor. Allosteric inhibitor makes a system more rigid and stable and the inhibitor binding to protease more firm.

Key words: MM-PBSA, binding free energy, HIV-1 protease, molecular fragments, allosteric inhibitor