Modelling and docking studies on Seryl tRNA synthetase of Plasmodium falciparum 3D7 as a potential drug target

Aim. Multidrug resistant strain Plasmodium fakiparum 3D7 (Pf), is the main causative organism of cerebral malaria. One strategy to over come resistance involves the inhibition of essential enzymes from the metabolic network of P falciparum. Pf Seryl tRNA synthetase (Pf StRNAse) is an enzyme involved in the amino acylation of protein translation. Inhibition of this enzyme prevents amino acylation. This study includes an Insilco approach using modelling and docking of Pf StRNAse protein with available antimalarial drugs from the ZINC database for the prediction of potent drug. Methods. Modeller 9.10 was utilized to generate the three dimensional structures of Pf StRNAse protein, and the 3D model Pf StRNAse protein was validated using PROCHECK. Virtual screening was performed by docking inhibitors obtained from the ZINC Database to the active site of the Pf StRNAse protein using Autodock software. The docked inhibitors were subjected to Lipinski's Rule of Five, and ADMET (absorption, distribution, metabolism, excretion and Toxicity) to evaluate the pharmacological, biological and ADME activity. Results. Homology model of Pf StRNAse was constructed using the X-ray structures of C. albicans Seryl tRNA synthetase (PDB code: 3QNE) as template, by comparative protein modelling principles. The quality of the generated 3D model was evaluated via the Ramachandran plot using PROCHECK. Docking studies of the antimalarial drugs form the ZINC database using Autodock has resulted eight inhibitors with least binding energy. The molecules were subjected to ADMET analysis. Conclusion. The present study suggests the essentiality of Pf StRNAse in the metabolism of the parasite and the mechanism of its interaction with the inhibitor as a potential drug target.