Design of a folding inhibitor of the HIV-1 Protease

Being HIV–1–PR an essential enzyme in the viral life cycle, its inhibition can control AIDS. Because the folding of single domain proteins, like HIV–1–PR is controlled by local elementary structures (LES, folding units stabilized by strongly interacting, highly conserved amino acids) which have evolved over myriads of generations to recognize and strongly attract each other so as to make the protein fold fast, we suggest a novel type of HIV–1–PR inhibitors which interfere with the folding of the protein: short peptides displaying the same amino acid sequence of that of LES. Theoretical and experimental evidence for the specificity and efficiency of such inhibitors are presented.