Overview of the PfAldolase–TRAP druggable pockets. a Potential ligand-binding pockets in PfAldolase. Eight pockets were identified in the cocrystal structure of aldolase bound to TRAP (PDB ID: 2pc4 ). Aldolase is shown as a ribbon coloured in a smooth gradient from blue at its N-terminus to red at its C-terminus. TRAP is shown as a green
ball-and-stick model. Only pockets 3, 6 and 8 are displayed because these three were targeted by the design with VLS since they are contacted by three non-conserved residues within aldolase—N51, E85, L117 (green balls-and-sticks)—as well as by the TRAP peptide. b Plot of the surface area (Å2) vs volume (Å3) for the eight pockets. Pockets 1, 2 and 3 fall within the 100–500 Å2/3 area/volume range, which is the usual area/volume for most FDA-approved drugs, following Lipinski’s rule of five .