The Computational Analysis ofPlasmodium falciparumHeat Shock Proteins Reveals an Interplay with Polyamines

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, 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. MD shows 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. Author’s summary The emanation and spread of Plasmodium parasites that are resistant to antimalarial therapy is one of the main problems in the treatment of malaria. This is a result of the Plasmodium parasite’s ongoing evolution and the creation of novel strategies for surviving drug toxicity. Studies of antimalarial drug development have been focused on polyamine biosynthesis by targeting precursors such as ornithine decarboxylase, adenosylmethionine decarboxylase, and spermidine synthase and protein-protein interactions between Plasmodium falciparum chaperones spotting out Hsp90, Hsp70, and Hsp40 as potential targets with little attention being paid to the interaction between polyamines and molecular chaperones. Therefore, to study these interactions the binding sites of all 3D structures were identified using SiteMap, and a docking was performed using the Schrödinger software with OPLS4 force field and XP.