For TbPTR1, we evaluated targeting the two subpockets, C and D, adjacent to the main biopterin binding site (Fig. and). Subpocket C (Fig. ) is predominantly hydrophobic flanked by the indole ring of Trp221, and features polar spots created by the backbone carbonyl oxygen of Trp221, His267 and the Ala268 C-terminus. Subpocket D (Fig. ), forming an entrance to the pocket, is surrounded by mostly hydrophobic residues. Notably, Trp221 flanks and divides the TbPTR1 pocket into subpockets C and D and adopts a similar conformation in the available crystal structures (see Fig. , SI), though some movement of the side-chain can be observed depending on the occupancy of subpocket C, as discussed Construction of the virtual compound library of compounds with designed linkers. A library of compounds containing the two fragments -2-aminobenzothiazole and 3,4-dichlorophenyl -connected by a series of linkers was designed computationally (Fig. ).