原子与分子物理学报2011，Vol.28Issue(1)：11-16,6.DOI:10.3969/j.issn.1000-0364.2011.01.003
Asp25质子化有利于HIV-1蛋白酶与抑制剂GRLO2O31结合
Protonation of Asp25 of HIV-1 protease stabilizes its binding to the inhibitor GRL02031
摘要
Abstract
GRL02031 is an inhibitor of the aspartate protease of HIV-1 and a potential therapeutic agent for AIDS. Determining the protonation state of Asp25/Asp25' in the protease-GRL02031complex (PR-031) is critical for understanding the binding mechanisms between the enzyme and the inhibitor and predicting the effects of mutations on drug sensitivity. Five-nanosecond molecular simulation was performed to analyze the effects of the four most possible protonation states of the aspartate residue on the dynamics of PR-031 binding. Relative binding free energies were calculated using the molecular mechanics/Possion-Boltzman surface area (MM-PBSA) method. The results showed that the OD2 protonation state of Asp25 in chain A is most favorable for the binding is therefore the most probable state. Moreover, analysis of hydrogen bonding on the water molecule that mediates PR-031 binding showed that the water molecule was the most stable under this protonation state. The study provides theoretical guidance for designing high affinity inhibitors and understanding mutation-induced drug resistance.关键词
HIV-1蛋白酶/分子动力学/MM-PBSA方法/结合自由能/质子化分类
生物科学引用本文复制引用
伊长虹,陈建中,朱通,张庆刚..Asp25质子化有利于HIV-1蛋白酶与抑制剂GRLO2O31结合[J].原子与分子物理学报,2011,28(1):11-16,6.基金项目
国家自然科学基金(10874104) （10874104）
山东省自然科学基金(Z2007A05) （Z2007A05）
