Hydrogen-bond interactions between bases (base pairing) are the largest contributors to the stability of the DNA duplex, as indicated by the diagonal elements in Fig. . Among these interactions, the G⋅⋅⋅C pairing is much stronger than the A⋅⋅⋅T pairing due to the presence of more hydrogen bonds in G⋅⋅⋅C. On average, the interaction energy is -27.5 kcal/mol for the G⋅⋅⋅C pairing and -10.4 kcal/mol for the A⋅⋅⋅T pairing in the gas phase. For comparison, the best available computational estimates of binding energies for isolated G⋅⋅⋅C and A⋅⋅⋅T pairs are -30/-32 kcal/mol and -15/-17 kcal/mol, respectively, depending on the computational methodology (see Table ). To a large extent, this difference originates from the fact that the geometry of the pair in the DNA is perturbed compared to its geometric ground state. In solution, the net average effect of base pairing is even smaller, with G⋅⋅⋅C and A⋅⋅⋅T pairs contributing just -13.3 kcal/mol and -3.9 kcal/mol, respectively, to the stability of the DNA duplex.