Solvent interactions with n ring systems in proteins

The interaction of water molecules with apolar amino acids isan important aspect of the hydrophobic effect and hence of proteinfolding. Our distributed multipole electrostatic model for waterinteracting with phenylalanine dipeptides shows that minimumenergy sites exist above the aromatic ring such that a solventmolecule can interact with the electrons, but only when thissite is not blocked by mainchain atoms or disturbed by main-chainpolar atoms. This is consistent with the experimental evidenceof others that water can hydrogen bond to aromatic n electrons.In contrast, our analysis of solvent interactions with phenylalanineresidues based on 48 high-resolution, well-refined protein structuresshows that the dominant interaction of solvent molecules iswith the edge of the ring and not with the 7i electrons. Asthe faces of phenylalanine rings tend to be buried, and solventinteractions with neighbouring polar atoms are more favourable,the interaction of water molecules with the faces of aromatic rings appears not to occur frequently in proteins