Automated calculation of docking of artemisinin to heme

Abstract.

We report automated molecular docking of artemisinin to heme. The effects of atomic charges, and ligand and heme structures on the docking results were investigated. Several charge schemes for both artemisinin and heme, artemisinin structures taken from various optimization methods and X-ray data, and five heme models, were employed for this purpose. The docking showed that artemisinin approaches heme by pointing O1 at the endoperoxide linkage toward the iron center, a mechanism that is controlled by steric hindrance. This result differs from that reported by Shukla et al. which suggested that heme binds with artemisinin at the O2 position. The docking results also depended on the structures of both artemisinin and heme. Moreover, the atomic charges of heme have a significant effect on the docking configurations.