<i>In-silico</i> techniques offer a fast, accurate, reliable, and economical approach to studying the molecular interactions between compounds and proteins. In this study, our main aim is to use <i>in-silico</i> techniques as a rational approach for the prediction of the molecular drug targets for luteolin against <i>Plasmodium falciparum</i>. Multi-target molecular docking, 100 nanoseconds (ns) molecular dynamics (MD) simulations, and Molecular Mechanics-Generalized Born Surface Area (MM-GBSA) binding free energy calculations were carried out for luteolin against dihydrofolate reductase thymidylate synthase (<i>Pf</i>DHFR-TS), dihydroorotate dehydrogenase (<i>Pf</i>DHODH), and falcipain-2. The native ligands of each protein were used as a reference to evaluate the performance of luteolin. Luteolin outperformed the native ligands of all proteins at molecular docking and MD simulations studies. However, in the MM-GBSA calculations, luteolin outperformed the native ligand of only <i>Pf</i>DHFR-TS but not <i>Pf</i>DHODH and falcipain-2. Among the studied proteins, the <i>in-silico</i> approach predicted <i>Pf</i>DHFR-TS as the most favorable drug target for luteolin.Communicated by Ramaswamy H. Sarma.
Authors: James H. Zothantluanga, Abd. Kakhar Umar, Keerthic Aswin, Sanchaita Rajkhowa, Dipak Chetia
DOI: https://doi.org/10.1080/07391102.2023.2263875
Publish Year: 2023
