Docking studies of structurally diverse antimalarial drugs targeting PfATP6: no correlation between in silico binding affinity and in vitro antimalarial activity.

PfATP6, a calcium-dependent ATPase of Plasmodium falciparum, is considered the putative target of the antimalarial drug artemisinin and its derivatives. Herein, the 3D structure of PfATP6 was modeled on the basis of the crystal structure of SERCA 1a, the mammalian homologue. Model validation was achieved using protein structure checking tools. AutoDock4 was used to predict the binding affinities of artemisinin (and analogues) and various other antimalarial agents for PfATP6, for which in vitro activity is also reported. No correlation was found between the affinity of the compounds for PfATP6 predicted by AutoDock4 and their antimalarial activity.