In silico evaluation of heat shock proteins reveals an interplay with polyamines as a survival strategy for the Plasmodium falciparum

Abstract

The current drugs available in the market are not effective due to growing numbers of resistance to the causative agent of malaria. There are various Plasmodium parasites, of which Plasmodium falciparum is the main cause of morbidity and mortality reported worldwide. Therefore, there is an urgent need to come up with an innovative and effective treatment for this disease. Polyamines play a major role in the parasite’s well-being and growth, while heat shock proteins keep the proteomics of the parasite in good shape. In this study, an in silico analysis of the interaction between putrescine, spermidine, spermine, and heat shock proteins was carried out to establish the binding site for drug discovery. Computational tools such as Bioedit, PROCHECK, KNIME Hub, and Schrodinger were used. The results revealed interactions between polyamines and heat shock proteins with glutamine and aspartic acid being common amino acids where interaction occurs between the chaperones and polyamines. Molecular dynamics showed a strong interaction between PfHsp70-1 and putrescine, but the best interaction is observed for PfHsp70-1 and spermidine. Based on these results, a follow-up study will be conducted to establish the synthesis of drugs that will be used as targets for both polyamines and heat shock proteins to eradicate malaria.