Noncovalent interactions between hydroxylated polycyclic aromatic hydrocarbon and DNA: Molecular docking and QSAR study

Polycyclic aromatic hydrocarbons (PAHs) can be hydroxylated by CYP450-oxidases (1A1 and 1B1 mainly) and may cause DNA damage and cancer. However, the mechanism of such interactions has not been fully understood. In this study, an integrated molecular docking and QSAR approach was employed to further investigate the binding interactions between hydroxylated PAHs (HO-PAHs) and calf thymus DNA (CT-DNA). Molecular docking, hydrogen-bonding, hydrophobic and pi-pi interactions were observed to be characteristic interactions between HO-PAHs and DNA. An optimum QSAR model with good robustness and predictability was developed based on the molecular structural parameters calculated by the density function theory and partial least squares. Additionally, the developed QSAR model indicated that the molecular size, polarizability and electrostatic potential of HO-PAHs were related to the binding affinities to DNA. (C) 2011 Elsevier B.V. All rights reserved.Polycyclic aromatic hydrocarbons (PAHs) can be hydroxylated by CYP450-oxidases (1A1 and 1B1 mainly) and may cause DNA damage and cancer. However, the mechanism of such interactions has not been fully understood. In this study, an integrated molecular docking and QSAR approach was employed to further investigate the binding interactions between hydroxylated PAHs (HO-PAHs) and calf thymus DNA (CT-DNA). Molecular docking, hydrogen-bonding, hydrophobic and pi-pi interactions were observed to be characteristic interactions between HO-PAHs and DNA. An optimum QSAR model with good robustness and predictability was developed based on the molecular structural parameters calculated by the density function theory and partial least squares. Additionally, the developed QSAR model indicated that the molecular size, polarizability and electrostatic potential of HO-PAHs were related to the binding affinities to DNA. (C) 2011 Elsevier B.V. All rights reserved