MOLECULAR MODELLING AND MOLECULAR DYNAMICS STUDIES OF SPECT PROTEIN OF PLASMODIUM FALCIPARUM AND IN SILICO SCREENING OF LEAD COMPOUNDS

摘要

Malaria has been a major life threatening mosquito borne disease. Unavailability of any effective vaccine and recent emergence of multi drug resistant strains of malarial pathogen?Plasmodium falciparum?continues to cause persistent deaths in the tropical and sub-tropical region. As a result, there is a growing demand for new targets for more effective anti-malarial drugs.?A novel microneme protein, named sporozoite microneme protein essential for cell traversal (SPECT), is produced by the liver-infective sporozoite of the malarial parasite. In the present study, the 3D conformation of Plasmodium falciparum SPECT (PfSPECT) protein was predicted using homology modelling and refined by 50 nanoseconds of MD simulation. The overall quality of the model was validated using PROCHECK and ERRAT. The PROCHECK results showed 91.4% of backbone angles were in the allowed region and ERRAT score of 85.9% suggested a high quality model. All docking calculations were performed using the “Extra Precision” (XP) mode of Glide docking. A database of 2,76,784 biogenic compounds was used for virtual screening, out of which 164 were identified as hits. Further, these compounds were analysed on the basis of docking and MM-GBSA scores and per residue interactions calculated. Molecular dynamics simulation studies were performed on two best protein-ligand complexes to check their stability. Ligand 1, ZINC03851216 depicted a stable hydrogen bond with Asn 99 residue on the protein and the complex stabilized after 10ns during the 50ns simulation time. Our data shows compelling indication that proposed ligands hold considerable potential for further experimental evaluation.