Non-Watson−Crick Base Pairing in RNA. Quantum Chemical Analysis of the cis Watson−Crick/Sugar Edge Base Pair Family

Large RNA molecules exhibit an astonishing variability of base-pairing patterns, while many of the RNA
base-pairing families have no counterparts in DNA. The cis Watson−Crick/sugar edge (cis WC/SE) RNA
base pairing is investigated by ab initio quantum chemical calculations. A detailed structural and energetic
characterization of all 13 crystallographically detected members of this family is provided by means of B3LYP/6-31G** and RIMP2/aug-cc-pVDZ calculations. Further, a prediction is made for the remaining 3 cis WC/SE base pairs which are yet to be seen in the experiments. The interaction energy calculations point at the
key role of the 2‘-OH group in stabilizing the sugar−base contact and predict all 16 cis WC/SE base-pairing
patterns to be nearly isoenergetic. The perfect correlation of the main geometrical parameters in the gas-phase optimized and X-ray structures shows that the principle of isosteric substitutions in RNA is rooted
from the intrinsic structural similarity of the isolated base pairs. The present quantum chemical calculations
for the first time analyze base pairs involving the ribose 2‘-OH group and unambiguously correlate the structural
information known from experiments with the energetics of interactions. The calculations further show that
the relative importance and absolute value of the dispersion energy in the cis WC/SE base pairs are enhanced
compared to the standard base pairs. This may by an important factor contributing to the strength of such
interactions when RNA folds in its polar environment. The calculations further demonstrate that the Cornell
et al. force field commonly used in molecular modeling and simulations provides satisfactory performance
for this type of RNA interactions.