Molecular simulations and docking studies for evaluating the pharmacokinetic properties of microalgal compounds targeting HIV-2 GP120

Abstract

Molecular docking and molecular dynamics (MD) simulations were performed to investigate the interactions between HIV-2 GP120 and marine algal-derived compounds. Using the CHARMM force field and AutoDock software, seven microalgal ligands were screened, among which Quinazolin-4(3H)-one exhibited the strongest binding affinity of −9.5 kcal/mol against the HIV-2 GP120 receptor (PDB ID: 5CAY). The MD simulations confirmed the structural stability of the Quinazolin-4(3H)-one–GP120 complex with an average RMSD of 1.5–2.0 Å over 103 frames, indicating minimal conformational fluctuations during the simulation period. Furthermore, ADMET analysis revealed 99% predicted human intestinal absorption, no Lipinski’s rule violations, and favourable bioavailability (0.55), suggesting strong drug-like behavior. These quantitative results support the selection of Quinazolin-4(3H)-one as the most promising compound among the tested ligands. Overall, this study provides simulation-based insights into ligand stability, pharmacokinetic performance, and receptor interactions, offering a potential framework for designing novel inhibitors targeting the HIV-2 GP120 viral entry mechanism.