Structure preparation, analysis and molecular docking simulations. The Maestro suite 2015-2 was used in all the calculation steps described below. The OPLS 2005 force field (the default force field when the study was started) was used in the preparation process. The molecular structures of receptors and chemical compounds were prepared similarly to those reported previously (see the details in SI). ADMET properties of the prepared compounds were evaluated with the QikProp tool of the Maestro suite and PAINS filtering was performed (more details in SI). Docking grids of size 40 Å x 40 Å x 40 Å centered on Phe97 for TbPTR1 and on Phe113 for LmPTR1, were calculated, with internal boxes of size 15 Å x 15 Å x 15 Å. The sizes were increased from the default values to account for the relatively large PTR1 pocket and considering the placement of ligands in different subpockets. Molecular docking simulations were performed using the Glide software . Standard settings for ligand van der Waals radii were kept. After initial tests, the SP docking protocol was used. The docking method was validated by redocking and cross-docking simulations (ligand RMSDs are provided in Tab. S11, SI). Ligands were treated as flexible; nitrogen inversions and ring conformations were sampled. Biased sampling was only performed for amide torsions, which were penalized if in a non-planar conformation. Epik state penalties were added to the docking score and the planarity of conjugated π-groups was enhanced. 20 poses were subjected to post-docking energy minimization with a pose-rejection threshold of 0.5 kcal/mol and up to 10 final docking solutions were retained. In addition, the docking procedure used a special treatment of halogen atoms as halogen-bond donors. The poses for each ligand were sorted based on the docking score, and further analyzed as described in the Results. It is worth noting that the docking scores are not accurate estimates of binding free energy, so poses other than the top-ranked one (according to the score) were considered as probable binding modes. If not otherwise noted, the three top poses for each compound were subjected to a more detailed analysis and visual inspection.