QSAR study of antimalarial activities and artemisinin-heme binding properties obtained from docking calculations.

The quantitative structure-activity relationships (QSAR) between antimalarial activities and artemisinin-heme binding properties were studied by means of docking calculations. Automated molecular dockings of 30 artemisinin derivatives to heme revealed a significant relationship between biological activity and binding energy (ra ˇ0:93) and less significantly with the O1-Fe distance (raˇ0:55). The QSAR models were constructed and the predicted biological activities were in good agreement with the corresponding experimental values. The docking also showed that artemisinin compounds approach heme by pointing O1 at the endoperoxide linkage toward the iron center, a mechanism controlled by the steric hindrance.