Several nonpeptide small molecules were designed as potential inhibitors of
HIV protease and their structures were constructed by computer-aided
molecular modeling and docked iwo the active site of HIV protease. Models of
the complexes of inhibitors and the HIV protease were refined using nonbonded
and H-bonding terms. The refined energy of selected complexes
showed that the designed inhibitors fitted tightly into the active site of receptor
cavity. The structure of the designed inhibitor (HI-082) was superimposed on
the molecule of haloperidol (which has been reported to have anti-HIV protease
activity) and it was found that they share a number of common structural
features. These results showed that these small nonpeptide molecules interact
strongly with the HIV protease and may therefore inhibit its action in which
case they would be potential anti-AIDS agents