A critical analysis of the binding pocket of Plasmodium falciparum Phosphatidylinositol-4-kinase enzyme

The Plasmodium falciparum phosphatidylinositol 4-kinase type III beta (PfPI4KIIIβ), a protease kinase enzyme, has been shown to be vitally important for the survival of the malaria parasite, both in the host and the vector. However, the lack of the three-dimensional structure and the full structural characterisation of its binding pocket limits its utility and subsequently the development of new, selective, and highly efficacious inhibitors. Thus, the current study is employing a homology modelling and docking strategy in analysing the binding site morphology and key amino acids that are involved in ligand-substrate complex formation. Our results reveal a homology model whose stability is confirmed by Ramachandran plots and RMSD. Furthermore, docking a few reported PfPI4KIIIβ inhibitors on this model revealed that the binding pocket of PfPI4KIIIβ is hydrophobic and prefers ligands that adopt a twisted conformation. Based on this analysis it can be concluded that these may possibly be the key amino acids whose interaction with the ligands are influenced by the presence of certain functional groups present in a ligand.