Electronic, spectroscopic, molecular docking and molecular dynamics studies of neutral and zwitterionic forms of 3, 4-dihydroxy-l-phenylalanine: A novel lung cancer drug

• Published in: Journal of molecular structure Vol. 1260; p. 132844
• Main Authors: Koyambo-Konzapa, Stève-Jonathan, Premkumar, R., Berthelot Saïd Duvalier, Ramlina Vamhindi, Gilbert Yvon, Mbesse Kongbonga, Nsangou, Mama, Benial, A. Milton Franklin
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 15.07.2022
• Subjects: DFT calculations; Lung cancer; Molecular docking; Molecular dynamics; Neutral and zwitterion l-dopa; Molecular dynamics; Lung cancer; Neutral and zwitterion l-dopa; DFT calculations; Molecular docking
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2022.132844

•The ground state optimizations of neutral and zwitterion l-DOPA molecules were carried out.•The experimental and theoretical wavenumbers were compared.•The NBO analysis indicates the intra and intermolecular interactions in studied molecules.•Molecular docking predicts the inhibitory nature of l-DOPA molecules against lung cancer.•Molecular dynamics simulations were used to validate the obtained docking poses. The 3, 4-dihydroxy-l-phenylalanine (L-DOPA) is used as an effective drug for the treatment of Parkinson's disease and also used as a precursor of many alkaloids. In the present study, the most stable optimized structures of l-DOPA in neutral and zwitterionic forms were predicted by the B3LYP functional method with cc-pVTZ basis set. The theoretical vibrational frequencies were assigned based on the potential energy distribution calculations using VEDA 4.0 and compared experimentally with the available FT-IR and Raman data. The lack of negative values in the calculated vibrational frequencies implies that the optimized geometries of the studied molecules are located at the local minima on the potential energy surfaces. The π→ π* and the n→ π* electronic transitions of the l-DOPA molecules were predicted from the theoretically simulated ultraviolet-visible spectra obtained in COSMO as a model of solvation. The frontier molecular orbitals are plotted, and the related molecular properties are calculated and discussed. The Mulliken atomic charge distribution calculations and the molecular electrostatic potential surfaces were simulated to confirm the reactive sites of the molecules under consideration. The natural bond orbital (NBO) analysis proves the bioactivity of each form of l-DOPA molecule. The molecular docking analysis reveals that the zwitterion l-DOPA molecule has a strong binding affinity towards the AKT targeted protein used in the treatment of lung cancer compared to the neutral l-DOPA molecule. The reliability of the docking results is validated from the data of the molecular dynamics simulations. Hence, the present study paves the way for designing the novel drugs for the treatment of lung cancer.