Molecular dynamics simulations of 2-amino-6-arylsulphonylbenzonitriles analogues as HIV inhibitors: interaction modes and binding free energies.

Molecular dynamics (MD) simulations in water environment were carried out on the HIV-1 reverse transcriptase (RT), and its complexes with one representative of each of three series of inhibitors: 2-amino-6-arylsulphonylbenzonitriles and their thio and sulphinyl congeners. Molecular Mechanics Generalized Born Surface Area (MM-GBSA) was used to calculate the binding free energy based on the obtained MD trajectories. Calculated energies are correlated to activity. A comparison of interaction modes, binding free energy, contributions of the residues to the binding free energy and H-bonds was carried out with the average structures. The results show that there exist different interaction modes between RT and ligands and different specific interactions with some residues. The higher binding affinity of the most potent inhibitor in the series of molecules under study is favoured by electrostatic interactions and solvation contribution.