DFT calculations were performed on nucleobase-nucleobase interaction profiles for both hydrogen bonding and stacking geometries. Figure shows the various types of profiles used in this fitting procedure. For hydrogen bonding profiles, initial structures were obtained from Jurečka et al . 10 unique base-pair combinations were used and capped with methyl groups at the N3 position for purines and N9 position for pyrimidines. See Supporting Information for a depiction of all combinations used. Geometries were then minimized at the ωB97X-V/cc-pVDZ 74 level of theory with Q-Chem 5.3. To establish the profiles, a local Cartesian coordinate system was established for each H-bonded pair, with the x-axis defined as the normalized average proton-acceptor distance, the ẑ-axis being orthogonal to the plane of the two bases, and the ŷ = ẑ × x. Distances along the profile (w.r.t. the equilibrium position)