Revealing Interaction Mode Between HIV‐1 Reverse Transcriptase and Diaryltriazine Analog Inhibitor

HIV-1 reverse transcriptase is a key enzyme playing an important role in the HIV-1 life cycle for the replication of the RNA genome into DNA form. Lys103Asn (K103N) mutant frequently is observed in HIV-1 reverse transcriptase. Therefore, a series of novel non-nucleoside reverse transcriptase inhibitors were designed and synthesized. In vitro experimental results show that diaryltriazine analogs have potent anti-HIV activity with moderate to high selectivity. In order to design anti-HIV drug, docking and molecular dynamics simulation were used to investigate the binding mode between ligand and HIV-1 reverse transcriptase. The results suggest that the analogs might have a similar interaction mechanism with HIV-1 reverse transcriptase. Then comparative molecular field analysis and comparative molecular similarity indices analysis were used to construct quantitative structure–activity models. These models were evaluated by eight test set compounds. These models are helpful in making quantitative prediction of their activity for new lead compounds before resorting in vitro and in vivo experimentation.