Quantum Mechanical Study of some Intercalating and Groove Binding Anticancer Drugs with AT and GC Base Pair of DNA Nucleobase

Anticancer drugs bind to DNA nucleobase pairs (AT and GC) through different binding modes such as intercalation, groove binding, covalent binding etc. Quantum mechanical method such as, density functional theory (DFT) is quite useful for computing the interaction energies of anticancer drug-DNA nucleobase complexes. In our study, we have selected some candidate anticancer drugs to investigate the interaction energies of drug-DNA complexes. Among the different binding modes of anticancer drugs, minor and major groove binding to DNA base pair are important ones; therefore, some anticancer drugs may be minor groove specific and some may be major groove specific. Such sequence-specific experimental studies for drug-DNA nucleobase complexes are very complicated; hence, theoretical calculations based on quantum mechanical theories are helpful. Here, we performed DFT calculations using M062X method and 6-311++G(d,p) basis set. Our results reveal that the stacked models of anticancer drugs-DNA nucleobase (AT and GC) complexes all show negative interaction energy values. Among all such complexes, the complex with the most negative interaction energy value indicates the most stable and favoured stacked system. The stacking interaction energies for anticancer drugs-DNA nucleobase (AT and GC) complexes could easily be reflected in the interaction energy plots.