HIV-1 protease is an important target of AIDS chemotherapy. Molecular dynamics simulations followed by MM-PBSA analyses were performed to study the binding of inhibitors BE4, BE5 and BE6 to HIV-1 protease. The results show that positioning of the fluorine atoms on the benzyloxy group of P₁/ of the inhibitors affects their binding free energies. Inhibitor-residue interactions calculated provide some insights into the mechanisms of enzyme-inhibitor binding. Our results indicate that the three inhibitors bind to HIV-1 protease in a very similar mode. The calculated data agree well with experimental findings.

Key words: HIV-1 protease, MM-PBSA/GBSA, molecular dynamics, binding free energy, inhibitor