Molecular Dynamics Simulations on the Role of Protonation States in HIV-1 Protease-Indinavir Complex

作者：Shi Shuhua; Hu Guodong; Chen Jianzhong; Zhang Shaolong; Zhang Qinggang

来源：Acta Chimica Sinica, 2009, 67(24): 2791-2797.

• molecular dynamics
• MM-PBSA
• binding free energy
• HIV-1 protease
• protonation state

The protonation state of Asp25/Asp25' in Protease-Indinavir (PR-IDV) complex is important for HIV-1 protease to study the binding mechanism and the drug resistance induced by the mutation in theory. The 5 ns molecular dynamic simulations have been performed for six possible protonation states, the influences on dynamics behavior and structure caused by different protonation states analyzed, and relative binding free energies calculated using the molecular mechanics/Possion-Boltzman surface area (MM-PBSA) method. The results show that the protonation state of OD2 from Asp25 in chain A is the most possible. The hydrogen bonds between the water molecule that plays a medium role and the PR-IDV complex were also analyzed, and the results show that the different states have not obvious influences on the medium role, which is different from our previous result on PR-BEA369 complex. It was expected that this study could provide a significative help for the high affinity inhibitor design and the mutation induced drug resistance research.

• 出版日期2009-12-28
• 单位山东师范大学; 山东建筑大学