HIV-1蛋白酶解聚型抑制剂的计算机辅助分子设计

COMPUTERAIDED MOLECULAR DESIGN OF HIV1 PROTEASE DISSOCIATIVE INHIBITORS

目的：探索性研究和设计ＨＩＶ１蛋白酶新型抑制剂—解聚型抑制剂。方法：计算机辅助药物设计的分子对接方法。结果：设计的一系列拟肽分子既可阻挠ＨＩＶ１ＰＲ二聚体的组装，又可抑制酶的活性。其中，ＰＰ３０可作为候选先导物。结论：解聚型抑制剂有望抑制突变的ＨＩＶ１ＰＲ。

AIM: To study exploratively a new type of HIV1 protease inhibitors, dissociative inhibitors. METHODS: The docking algorithm of computeraided 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 HIV1 PR homodimer but also to act on the activesite residues to inhibit the activity of the enzyme. The molecule PP30, Nphenylacetyl3,4dihydroxy3methyl2aminobutyryl{3carbamylethyl6isoquinolyl3,4dihydroxy5aminohexanoyl]}4(2benzoimidazolyl)2aminobutyric acid, has the lowest interaction energy and may be a hopeful lead structure. CONCLUSION: Dissociative inhibitors are expected to inhibit the mutant HIV1 PR.