Analyzing Interaction of Rhodacyanine Inhibitor 'MKT-077' with Plasmodium falciparum HSP70s.

Abstract

MKT-077 and its derivatives are rhodacyanine inhibitors that hold po-tential in the treatment of cancer, neurodegenerative diseases and malaria. These allosteric drugs act by inhibiting the ATPase action of heat shock proteins of 70kDa (HSP70). MKT-077 accu-mulates in the mitochondria and displays differential activity against HSP70 homologs. The four Plasmodium falciparum HSP70s (PfHSP70) are present in various subcellu-lar locations to perform distinct functions. In the present study, we have used bioinformatics tools to understand the interaction of MKT-077 at the ADP and HEW (2-amino 4 bro-mopyridine) binding sites on PfHSP70s. Our molecular docking experiments predict that the mi-tochondrial and endoplasmic reticulum PfHSP70 homologs are likely to bind MKT-077 with higher affinities at their ADP binding sites. Binding analysis indicates that the nature of the identified interactions is primarily hy-drophobic. We have also identified specific residues of PfHSP70s that are involved in interacting with the ligand. Information obtained in this study may form the foundation for the design and de-velopment of MKT-077-based drugs against malaria.