Hydrogen bonds from water molecules to aromatic acceptors in very high-resolution protein crystal structures

Short contacts of water molecules with the pi-faces of aromatic residues were studied in a set of 75 very high resolution (<1.1 A) protein X-ray crystal structures. For 18 water molecules found at distances to aromatic midpoints <3.5 A, it was attempted to assign the hydrogen bond configuration (without experimental knowledge of the H-atom positions) by inspection of the surrounding. For approximately one-quarter of the cases, evidence for an O-H...pi hydrogen bond was found, another one-quarter does not form such a hydrogen bond, and for the remaining half, no conclusive assignment could be made. The results confirm the relatively frequent occurrence of aromatic hydrogen bonding in biomolecular hydration, but also underline difficulties in hydrogen bond assignment without reliable knowledge of the H-atom positions.