In Silico study of carcinogenic o-Quinone metabolites derived from polycyclic aromatic hydrocarbons (PAHs)

Abstract

A computational density functional theory study on the structural and electronic properties of several polycyclic aromatic hydrocarbon (PAH) ortho-quinones was performed and the possible mechanism of DNA-adduct formation was analyzed to evaluate its thermodynamic viability. Molecular docking techniques were applied to examine the noncovalent interactions developed when a model PAH ortho-quinone intercalates between the DNA double helix. Quantum-chemical ONIOM (our Own N-layer Integrated molecular Orbital molecular Mechanics) calculations within the structure of a DNA fragment were carried out to evaluate the significant steps of noncovalent complex and covalent adduct formation. The solvent effect was also considered by employing a continuum solvation model. The present calculations suggest that initial noncovalent interactions of the PAH o-quinone within the DNA double helix could determine the feasibility of benzo[a]pyrene-7,8-dione-DNA covalent adduct formation, and that dispersion-corrected functionals are more suitable for locating the noncovalent complex. Copyright © 2012 John Wiley & Sons, Ltd.