COMPUTER-AIDED MOLECULAR DESIGN OF HIV-1 PROTEASE DISSOCIATIVE INHIBITORS

AIM: To study exploratively a new type of HIV-1 protease inhibitors, dissociative inhibitors. METHODS: The docking algorithm of computer-aided molecular design as described in this paper. RESULTS: A series of peptidomimetics have been designed, not only to act on the terminal segments to block the assembly of the HIV-1 PR homodimer but also to act on the active-site residues to inhibit the activity of the enzyme. The molecule PP30, N-phenylacetyl-3，4-dihydroxy-3-methyl-2-aminobutyryl-3-carbamylethyl-6-isoquinolyl-［2-(2'-hydroxy-cyclohexamethyl)-3，4-dihydroxy-5-aminohexanoyl］-4-(2-benzoimidazolyl)-2-aminobutyric acid, has the lowest interaction energy and may be a hopeful lead structure. CONCLUSION: Dissociative inhibitors are expected to inhibit the mutant HIV-1 PR.