Structures prediction of Plasmodium Falciparum Signal Peptide Peptidase (PfSPP) and identification of binding Site

Abstract

Malaria is a tropical parasitic disease caused by mosquitoes. Plasmodium falciparum is the species that causes the most human deaths compared to other species. Plasmodium which infects red blood cells will causes pathology and clinical manifestations in malaria sufferers. Plasmodium falciparum Signal Peptide Peptidase (PfSPP) is an important enzyme to infect red blood. I-TASSER (Iterative Threading ASSEmbly Refinement) has been used to predict the 3D structure of the PfSPP enzyme by modeling using proteins in databases. Based on data analysis such as Ramachandran plot, G-Factor, RMSD, Radius of gyration, and NAMD energy, model 5 is the best model of all I-TASSER structure prediction models. AutoLigand was used to predict the binding sites on this model and obtained 5 binding sites points with lowest free energy on each fill point. Binding sites 3, 4 and 5 have the largest volumes 345 Å3, 372 Å3, and 395 Å3 respectively so that they have potential to bind with both ligand mefloquine and primaquine with volume 330 Å3 and 333 Å3 respectively. Three binding sites have the potential to inhibit PfSPP so it cannot function properly and stop the invasion of the parasite's merozoite to other erythrocytes.