On the misincorporation of nucleotides opposite mutagenic cyclic 1,N-propanoguanine: A computational investigation.

The misincorporation properties of exocyclic DNA adduct, cyclic 1,N-propanoguanine with nucleobases have been investigated using DFT and DFT-D methods. Number of possible and stable mispairing conformations of cyclic 1,N-propanoguanine with A,T,G and C have been considered for our investigation. The single point energy calculations have been carried out at the M06/6-311++G**, ωB97XD/6-311++G** and MP2/6-311++G** levels on corresponding optimized geometries. The reaction enthalpy values were employed at the M06/6-31 + G* and ωB97XD/6-31 + G* levels. The energies have been compared among the cyclic 1,N-propanoguanine adduct with nucleobases to find the most stable conformer. The CPCM model was utilized on account of solvent phase and overall polarizability. The computed binding energies follow the order as CPr-Gua-G(2)(-23.2 kcal/mol) > CPr-Gua-C(1) (-16.1 kcal/mol) > CPr-Gua-A(2)(-10.6 kcal/mol) > CPr-Gua-T(2)(-9.6 kcal/mol) in the gas phase at M06 level, which indicates the guanine and cytosine are favorable for mispairing with the cyclic 1,N-propanoguanine adduct. The obtained results using computational tools are in good agreement with the experimental observation.