Drug Resistant Mechanism of Diaryltriazine Analog Inhibitors of HIV-1 Reverse Transcriptase Using Molecular Dynamics Simulation and 3D-QSAR

作者：Li, Zeng; Zhang, Hao; Li, Yixue^*; Zhang, Jian; Chen, Hai-Feng

来源：Chemical Biology & Drug Design, 2011, 77(1): 63-74.

DOI：10.1111/j.1747-0285.2010.01049.x

• diaryltriazine analog
• drug resistance
• HIV-1 reverse transcriptase inhibitor
• molecular dynamics simulation
• three-dimensional quantitative structure-activity relationship

Diaryltriazine inhibitors have highly potent and effective bioactivities for the wild type of HIV-1 reverse transcription. To design new drug of antimutant HIV-1 reverse transcriptase, the mechanism of drug resistance for four types of mutants was revealed. Molecular dynamics simulations suggest that Lys101, Leu100, Lys103, Tyr181, and Tyr188 are key residues. Different mutants of key residues may have different interaction modes and lead to different drug resistances. Then, CoMFA and CoMSIA methods were employed to construct 3D quantitative structure-activity relationship models. These models were evaluated by test set compounds. These models can be used to make quantitative prediction of their bioactivities for lead compounds before resorting to in vitro and in vivo experimentation.

• 出版日期2011-1
• 单位上海交通大学; 上海生物信息技术研究中心