In silico analysis of plasmodium falciparum CDPK5 protein through molecular modeling, docking and dynamics

Abstract Calcium-Dependent Protein Kinase 5 (CDPK5) protein is one of the family members of a calcium-dependent protein kinase that is found in plants and some species of protozoa which includes Plasmodium falciparu m (Pf), the pathogen responsible for malaria. CDPKs regulate many biological processes in Apicomplexans such as Plasmodium, Toxoplasma or Cryptosporidium . The study addresses the similarity in sequences and evolutionary relationship of CDPK5 across Apicomplexans. Further, the three-dimensional structural conformation of PfCDPK5 is generated through homology modeling. Molecular dynamics simulation of the homology model for a time interval of 40 ns resulted in a stable conformation of the PfCDPK5 protein. Inhibitor identification was carried out from computational screening of known anti-malarial compounds. The reliability of the binding mode for the best inhibitor compound MMV687246 was validated through a complex molecular dynamics study. This findings advocates that MMV687246 from Pathogen Box as the best inhibitor against PfCDPK5 protein and can be considered for experimental validation study in future.