In Silico Study of Bioactive Compounds from Morinda lucida as Potential Inhibitors of Plasmodium falciparum Glutathione Reductase Using PASS Prediction, ADMET Analysis, Molecular Docking, DFT, and Molecular Dynamics Simulations

Abstract

The current study employed integrated in silico methods to assess the biological activity of phytochemical compounds from Morinda lucida as potential inhibitors of P. falciparum Glutathione Reductase (PfGR). In all, 100 phytochemicals were screened using the Prediction of Activity Spectra for Substance (PASS). Then, Pharmacokinetics and Toxicity assessment were conducted using the SwissADMET and pkCSM servers. Subsequently, the selected phytochemicals were subjected to Molecular Docking, Density Functional Theory (DFT) studies, Molecular Dynamics Simulation, and MM/PBSA Binding Energy Analysis. The molecular docking with DFT study indicated that the 4-Hydroxyphenyl-3-nitrobenzoate (B4) showed a smaller HOMO-LUMO energy gap suggests higher chemical reactivity and lower kinetic stability, and a strong binding affinity (-8.3 kcal/mol) to the target protein in comparison to Chloroquine (-5.9 kcal/mol) and Lumefantrine (-7.3 kcal/mol). Thus, the 4-Hydroxyphenyl-3-nitrobenzoate (-8.3 kcal/mol) B4 may serve as a preliminary candidate identified via in silico screening and can also be investigated for antimalarial drug development.