Revelation of potential drug targets of luteolin in Plasmodium falciparum through multi-target molecular dynamics simulation studies.

In-silico 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 in-silico techniques as a rational approach for the prediction of the molecular drug targets for luteolin against Plasmodium falciparum . 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 ( Pf DHFR-TS), dihydroorotate dehydrogenase ( Pf 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 Pf DHFR-TS but not Pf DHODH and falcipain-2. Among the studied proteins, the in-silico approach predicted Pf DHFR-TS as the most favorable drug target for luteolin.Communicated by Ramaswamy H. Sarma.