Prediction of the binding model of HIV-1 gp41 with small molecule inhibitors.

Despite the synthetic peptides inhibit HIV-1 entry; its application of this peptide therapy may be limited due to the high cost of the peptide production and lack of its oral availability. Thus, it is necessary to identify the small molecule inhibitors reacting with the same or overlapping target sites on gp41 recognizing the antiviral peptides. In this work, a small inhibitor (TP1) is docked into the hydrophobic grooves of gp41 by using AutoDock software, resulting in five alternative energetically favorable models. The data from other studies were used to define our preferred models. We found that only one binding mode is supported by the experimental evidence. The model could be used to design more effective HIV-1 inhibitors targeted to the HIV-1 gp41 core structure.