Fig. 1.
Models of the artificially evolved HIV PR variants. The cocrystal structure of the D25N HIV PR/p6 peptide complex (Prabu-Jeyabalan, Nalivaika, and Schiffer 2002) was modified by molecular modeling (using the SYBYL software package) as follows. The ‘‘native’’ p6 peptide was mutated into the novel NRPDYLLFAE peptide substrate (derived from TNF-α); the P9S and I50L mutations were made (A). The new complex was energy minimized. The Q7L (B), W6R, F53S, N83I, I93N (C), and L5F (D) mutations, which are also associated with changes in substrate specificity, are modeled on the unaltered D25N HIV PR/p6 structure.