Computational design and experimental study of tighter binding peptides to an inactivated mutant of HIV-1 protease.

ABSTRACT: Drug resistance in HIV-1 protease, a barrier to effective treatment, is generally caused by mutations in the enzyme that disrupt inhibitor binding but still allow for substrate processing. Structural studies with mutant, inactive enzyme, have provided detailed information regarding how the substrates bind to the protease yet avoid resistance mutations; insights obtained inform the development of next generation therapeutics. Although structures have been obtained of complexes between substrate peptide and inactivated (D25N) protease, thermodynamic studies of peptide binding have been challenging due to low affinity. Peptides that bind tighter to the inactivated protease than the natural substrates would be valuable for thermodynamic studies as well as to explore whether the structural enve

SUBMITTER: Altman MD 

PROVIDER: S-EPMC2802840 | biostudies-literature | 2008 Feb

REPOSITORIES: biostudies-literature