Water-mediated base pairs in RNA:: A quantum-chemical study

We have studied the geometric and energetic properties of the six water-mediated base pairs WUC, WGA, WUA, WUU, WUG, WGG, (W: water) and of the related water-free complexes by quantum-chemical calculations including electron correlation at the MP2/6-3G(d,p)//HF/6-31G(d,p) and B3LYP/G-31G(d,p) levels. In the water-mediated WUC, WGA,and WUU base pairs, water is both donor and acceptor of ii-bonds, and for these complexes the calculated hydrogen bonding patterns are close to the experimental ones within the RNA helix and allow cooperative effects within the H-bond network. The geometries of these base pairs are obviously almost not affected by the nucleic acid and solvent environment. Therefore, they can be considered as structurally autonomous building blocks of RNA. In the optimized structure of the WUA base pair water still links the two bases, yet the H-bond pattern deviates somewhat from the one in the RNA crystal structure and it is not cooperative. Therefore, we classify the WUA base pair as an intermediate case. In WUG and WGG pairs, water is twice acceptor or twice donor. These complexes are not structurally autonomous, but apparently have to be stabilized by additional interactions with the surrounding nucleic acid and solvent. For the UG pair a water-mediated C5-H5(U). . . O6(G) contact involving an alternative water molecule (371) in the major groove is important and leads to a base pair geometry resembling the experimental structure (W-371-UG). In the GG pair, short contacts to a backbone C5'-H5' donor group and to a further water molecule are likely to stabilize the experimental base pair geometry. Similar to exocyclic amino groups, water involved in base pairing induces nonplanar equilibrium geometries, yet except for one of the examples (WCA) the energy difference to the corresponding planar conformation is very small. Cooperative effects have been found to contribute between 9 and 13% at the MP2/HF level and between 8 and 20% at the B3LYP level to the total interaction energy of all water-mediated pairs except for WUA. WUC is the only example for which the absolute value of the total interaction energy per H-bond is significantly increasing in passing from the direct to the water-mediated pair.