Prediction of the binding mode between BMS-378806 and HIV-1 gp120 by docking and molecular dynamics simulation.

BMS-378806 is a newly discovered small molecule that effectively blocks the binding of CD4 with gp120. The binding mode of this kind of inhibitor remains unknown. In this paper, AutoDock 3.0 in conjunction with molecular dynamics simulation, accommodating the receptor's flexibility, was used to explore the binding mode between BMS-378806 and gp120. Two structures, Mode I and Mode II, with the lowest docking energy were selected as different representative binding modes. The analysis of the results from the molecular dynamics simulation indicated that the binding of BMS-348806 in Mode II is more stable. The average structure of Mode II was analyzed and compared with the experimental data. The conclusion was that BMS-378806 inserts the azaindole ring deeply into the PHE43 cavity and makes contact with a number of residues in the cavity, on the cavity and near the cavity. This study benefits the understanding of the mechanism of this kind of inhibitor and may provide useful information for rational drug design.