Molecular modelling of calcium dependent protein kinase 4 (CDPK4) from Plasmodium falciparum

Abstract

Malaria continues to be one of the most serious global health challenges. The increasing incidence of drug resistant Plasmodium strains has emphasised the need for urgent action in the development of new therapeutic strategies against this disease. Development of new drug targets is of vital importance in this regard. The recent availability of genomic information and the resultant observation that in many instances, protein kinases from parasitic protozoa are phylogenetically distant from those in humans has established this group of enzymes as potential drug targets in the Malaria parasite. In order to rationally design novel inhibitors and chemical tools exclusively targeting CDPKs, reliable molecular structures are needed. Structural Bioinformatics, specifically molecular modelling, can contribute immensely to improving access to structural information for these challenging targets. Here, a three dimensional structure of PfCDPK4 created by homology modelling is reported. Further, a model structure with computationally docked ATP is created. These structures will be used to facilitate the discovery and development of novel inhibitors and chemical proteomics tools for the study of this sub-family of proteins.