期刊
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
卷 45, 期 1, 页码 227-235出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2009.09.048
关键词
Molecular dynamics simulation; MM-PBSA; HIV-1 protease; Drug resistance
资金
- National Nature Science Foundation of China [10874104, 10474060, 10504017]
- Ministry of Education [206093]
- Nature Science Foundation of Shandong Province [Z2007A05]
- Shandong Province Foundation [2008BS01013]
The single mutations I50V, V82A and I84V are considered as the key residue mutations of the HIV-1 protease drug resistance. The rank of calculated absolute binding free energies using MM-PBSA method is in excellent agreement with experimental result. Enthalpic and entropic balance is analyzed to explain resistance in I50V and V82A having a higher entropic contribution than in the wild type (WT) complex. The reduced van der Waals energy explains the drug resistance of I84V to GRL-98065. Detailed binding free energies between GRL-98065 and individual protein residues are calculated to provide insights into the inhibitor-protein binding and drug-resistant mechanism. Our results show I50V and V82A have larger structural changes than I84V compared with WT. (C) 2009 Elsevier Masson SAS. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据