Figure 5
From: High-throughput profiling of point mutations across the HIV-1 genome
Application of the HIV-1 qHRG missense mutational profiling data to aid in CA drug design. (A) Surface representation of CA hexamer (PDB 3H47), with alternating CA monomers shown in light and dark grey, respectively. The CA binding pocket of PF-3450074 is colored in cyan. High-resolution inset view also provided highlighting inhibitor binding orientation (PDB 2XDE), with CA protein in light grey, inhibitor binding residues in cyan, and PF-3450074 in stick representation and colored by element with C in green, O in red, and N in blue. CA positions are labeled to show drug binding residues (black) and/or resistant positions (white). The small molecule chemical structure of PF-3450074 is provided with chemical moieties that occupy each CA sub-pocket labeled. (B) The log10 RC index for CA substitutions at positions involved in PF-3450074 binding (P1-P3) and the resistant positions (RP). The graphs are color-coded to represent a tolerant (green), attenuated (blue), or lethal (red) phenotype depending on the measured log10 RC index for each CA substitution. WT amino acid identities are horizontally labeled at the top of each graph, with substitution identities individually labeled for each entry.