Theoretical Models of Aspartic Proteases: Active Site Properties, Dimer Stability and Interactions with Model Inhibitors

Abstract

HIV-1 PR, an aspartic proteinase (AP), is recognized now as an important target for designing effective and selective drugs which could arrest the late stages in replication of HIV-1, the causative agent of AIDS.¹ Selectivity of such enzyme inhibitors is required in addition to high affinity. The most spectacular difference between HIV-1 PR, a retroviral enzyme, and the cellular AP, is the smaller size and dimeric structure of the former. The conservation of active site residues, Asp-Thr/Ser-Gly, seems to eliminate the ability to design selective active-site inhibitors for AP.² This is, however, achieved by accumulated experience with the construction of novel renin inhibitors.