Virtual Screening and Validation of Potential Lead Compound from the Malaria Box against Plasmodium Falciparum S7 and S19 Proteins

Authors: Mwangi HN, Onyango S, Omosa LK and Mulaa F*

DOI: 10.23880/oajpr-16000154

Volume 2, Issue 2

Abstract

Molecular docking is a computer based tool used in drug design, where predominant binding modes of a ligand with known three dimensional protein structures are predicted. This study addresses the possible ways of coming up with antimalarial drugs using computational chemistry methods. This approach which utilizes virtual screening is more advantageous as it is effective, affordable and less tedious as compared to the normal laboratory experimental biological assays and spectroscopic techniques for characterization of the compounds. Treatment of malaria has become complex due to the high rate of emergence of resistance exhibited by Plasmodium falciparum and mutations resulting from the parasite. To test the reliability of this model for future tests, compounds for this study were sourced from the Malaria Box containing compounds proven to have interesting activities against the malaria causing parasite, P. faliciparum. In the current study, three dimensional structures of twenty compounds fetched from the Malaria Box and of the ribosomal 40S proteins S7 and S19 were generated using structure predicting software. The potential of the selected compounds to dock and bind onto the ribosomal 40S proteins S7 and S19 proteins was accessed by calculating pose complex RMSD as well as its geometric shape complementarity score, approximate interface area, atomic contact energy, the 3d transformation, 3 rotational angles and 3 translational parameters applied on the ligand molecule, to test authenticity of the docking experiments. The compounds that showed best pose were considered active lead compounds. Using this model three out of several compounds from the Malaria Box confirmed the results that were obtained using laboratory experiments as evidenced from the low energy pose of the complex. The objectives of the experiment were accomplished as the Plasmodium falciparum proteins S7 and S19 models were generated, validated and the docked structures of the two proteins with the ligands generated. Through the research it was evident that the compounds in the malaria box library could be screened easily, quickly and perfectly to eliminate experimental false positives and negatives. These results could help expedite the process of bringing a more effective class of antimalarial drugs as the results show that they have activity against the proteins with further in vitro validation.

Keywords: Computation chemistry; proteins docking; malaria box; homology modeling; Plasmodium falciparu; RMSD

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