A Computational Study of Molecular Mechanism of Chloroquine Resistance by Chloroquine Resistance Transporter Protein of Plasmodium falciparum via Molecular Modeling and Molecular Simulations

Abstract

The molecular mechanism of chloroquine resistance by the chloroquine resistance transporter protein of Plasmodium sp. is explored using molecular modeling and computational methods. The key mutation, lysine(K)-76 to threonine(T) (LYS76THR) in the transporter protein pertains to increased recognition of the protonated forms of the antimalarial drug. Such enhanced affinity can promote drug efflux from host digestive vacuole, rendering aminoquinoline-based treatment ineffective.