SOLVENT INTERACTIONS WITH PI-RING-SYSTEMS IN PROTEINS

The interaction of water molecules with apolar amino acids is an impor tant aspect of the hydrophobic effect and hence of protein folding. Ou r distributed multipole electrostatic model for water interacting with phenylalanine dipeptides shows that minimum energy sites exist above the aromatic ring such that a solvent molecule can interact with the p i electrons, but only when this site is not blocked by main-chain atom s or disturbed by main-chain polar atoms. This is consistent with the experimental evidence of others that water can hydrogen bond to aromat ic pi electrons. In contrast, our analysis of solvent interactions wit h phenylalanine residues based on 48 high-resolution, well-refined pro tein structures shows that the dominant interaction of solvent molecul es is with the edge of the ring and not with the pi electrons. As the faces of phenylalanine rings tend to be buried, and solvent interactio ns with neighbouring polar atoms are more favourable, the interaction of water molecules with the faces of aromatic pi rings appears not to occur frequently in proteins.