Cys368 of the P loop and Cys510, the DFG-1 residue of the activation loop. Sequence and structural alignments of PfCLK3 and a set of 497 human kinases were completed using the resource KINCORE TM and the Molecular Operating Environment (MOE) (Fig. ). All cysteines within the P-loop of the human kinome set were selected in KINCORE and the structures of these kinases loaded and aligned with PfCLK3 in MOE. This analysis established that Cys510 (DFG-1) of PfCLK3 has 45 equivalent cysteines within the human kinome set, whereas Cys368 has only 2 (hCDK8 and hCDK19, Fig. ). Cys368 was therefore chosen as the more attractive nucleophilic residue for a covalent inhibitor to confer selectivity.