In silico methods such as molecular docking and molecular dynamic (MD) simulations have significant interest due to their ability to identify the protein-ligand interactions at the atomic level. In this work, different computational methods were used to elucidate the ability of some olive oil components to act as Neisseria adhesion A Regulatory protein (NadR) inhibitors. The frontier molecular orbitals (FMOs) and the global properties such as global hardness, electronegativity, and global softness of ten olive oil components (α-Tocopherol, Erythrodiol, Hydroxytyrosol, Linoleic acid, Apigenin, Luteolin, Oleic acid, Oleocanthal, Palmitic acid, and Tyrosol) were reported using Density Functional Theory (DFT) methods. Among all investigated compounds, Erythrodiol, Apigenin, and Luteolin demonstrated the highest binding affinities (-8.72, -7.12, and -8.24 kcal/mol, respectively) against NadR, compared to -8.21 kcal/mol of the native ligand based on molecular docking calculations. ADMET properties and physicochemical features showed that Erythrodiol, Apigenin, and Luteolin have good physicochemical features and can act as drugs candidate. Molecular dynamics (MD) simulations demonstrated that Erythrodiol, Apigenin, and Luteolin show stable binding affinity and molecular interaction with NadR. Further Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) analyses using the MD trajectories also demonstrated the higher binding affinity of Erythrodiol, Apigenin and Luteolin inside NadR protein. The overall study provides a rationale to use Erythrodiol, Apigenin, and Luteolin in the drug development as anti-adhesive drugs lead. Communicated by Ramaswamy H. Sarma.
Keywords: ADMET; DFT; MD simulations; NadR protein; molecular docking.