DFT simulation of Watson–Crick-like guanine–thymine mismatch in quaternary systems involving DNA bases

The aim of this work is to theoretically investigate the guanine–thymine mismatch in the presence of adenine–thymine and guanine–cytosine base pairs. At M06-2X/6-311++G(d,p) level, the absolute values of formation energy of quaternary systems increase by going from systems having enol form of guanine (G*) to those containing enol tautomer of thymine (T*). Moreover, the stacking between T* and purine bases, in comparison with pyrimidine bases, increases the stability of quaternary systems having T*. On the other hand, the stacking between G* and pyrimidine bases more stabilises systems involving G*. From a thermodynamic point of view, the quaternary systems containing G−T* can transform their geometries into systems having G*−T. To gain a better understanding of the influence of hydrogen bonds on the stability of systems, the atoms in molecules and natural bond orbital analyses are used to evaluate the strength of hydrogen bonds in the investigated systems.