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Genome-wide Mapping of Drug-DNA Interactions in Cells with COSMIC (Crosslinking of Small Molecules to Isolate Chromatin)
Published on: January 20, 2016
Noncovalent interactions between hydroxylated polycyclic aromatic hydrocarbon and DNA: molecular docking and QSAR
Fei Li1, Xuehua Li, Xiaoli Liu
1Key Laboratory of Coastal Zone Environment Processes, CAS, Shandong Provincial Key Laboratory of Coastal Zone Environment Processes, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai 264003, China.
Environmental Toxicology and Pharmacology
|October 19, 2011
Summary
Hydroxylated polycyclic aromatic hydrocarbons (HO-PAHs) bind to DNA through specific molecular interactions. Their binding affinity is linked to molecular size, polarizability, and electrostatic potential, as revealed by QSAR modeling.
Area of Science:
- Environmental Chemistry
- Toxicology
- Computational Chemistry
Background:
- Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants.
- CYP450-oxidases hydroxylate PAHs, forming HO-PAHs.
- HO-PAHs are implicated in DNA damage and carcinogenesis, but mechanisms are unclear.
Purpose of the Study:
- To investigate binding interactions between HO-PAHs and calf thymus DNA (CT-DNA).
- To elucidate the molecular mechanisms underlying HO-PAH-DNA interactions.
- To develop a predictive QSAR model for HO-PAH binding affinity.
Main Methods:
- Integrated molecular docking and Quantitative Structure-Activity Relationship (QSAR) approach.
- Density Functional Theory (DFT) for calculating molecular structural parameters.
- Partial Least Squares (PLS) regression for QSAR model development.
Main Results:
- Molecular docking revealed characteristic interactions: hydrogen-bonding, hydrophobic, and π-π interactions between HO-PAHs and CT-DNA.
- An optimal QSAR model with robust predictability was successfully developed.
- QSAR model indicated that molecular size, polarizability, and electrostatic potential correlate with HO-PAH binding affinities to DNA.
Conclusions:
- Specific molecular interactions govern HO-PAH binding to DNA.
- QSAR modeling provides a predictive tool for assessing binding affinities.
- Understanding these interactions is crucial for evaluating PAH-induced genotoxicity and cancer risk.
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