摘要
结晶水分子W301在几乎所有的HIV-1蛋白酶(HIV-1PR)和配体的晶体结构中出现.在HIV-1PR中A链天门冬氨酸残基Asp25质子化状态或B链Asp25质子化状态下,QM/MM模拟后MM-GBSA方法计算得到W301水分子在HIV-1PR/ABT-538结合中的自由能贡献分别为-16.88kJ/mol、-17.63kJ/mol,W301水分子在HIV-1PR/ABT-538的结合中起到了关键的作用.进一步分析发现W301水分子与HIV-1PR和ABT-538分别形成了两个、四个氢键.
The special water molecule W301 which bridges the flaps of PR and ABT - 538 is observed in almost all HIV- 1 PR- inhibitor complexes. In this work, molecular dynamics （MD） simulations employing a hybrid Quantum Mechanics/Molecular Mechanics （QM/MM） approach have been carried out to determine the binding free energy between W301 and HIV - 1 PR/ ABT - 538. The contributions of W301 to the binding free energy in HIV - 1 PR/ABT - 538 complex are - 16.88 k J/mol, - 17.63 k J/mol in two monoprotonation states for Asp25 （A） and Asp25 （B）, respectively. The water molecule W301 forms two hydrogen bonds with HW - 1 PR and forms four hydrogen bonds with ABT- 538 at the same time.
出处
《山东师范大学学报（自然科学版）》
CAS
2008年第4期32-34,共3页
Journal of Shandong Normal University(Natural Science)
基金
国家自然科学基金资助项目(10474060
10504017)
山东省自然科学基金资助项目(Q2006A06)
