π-effects have an important contribution to biological systems since they provide a significant amount of binding enthalpy. Neurotransmitters produce most of their biological effect by binding to the active site of a protein receptor. Pioneering work of Dennis A. Dougherty is a proof that such kind of binding stabilization is the effect of cation-π interactions of the acetylcholine  (Ach) neurotransmitter. The structure of acetylcholine esterase includes 14 highly conserved aromatic residues. The trimethyl ammonium group of Ach binds to the aromatic residue of tryptophan (Trp). The indole site provides a much more intense region of negative electrostatic potential than benzene and phenol residue of Phe and Tyr. S-Adenosyl methionine (SAM) can act as a catalyst for the transfer of methyl group from the sulfonium compound to nucleophile. The nucleophile can be any of a broad range structures including nucleic acids, proteins, sugars or C=C bond of lipids or steroids. The van der Waals contact between S-CH unit of SAM and the aromatic face of a Trp residue, in favorable alignment for catalysis assisted by cation-π interaction.
A great deal of circumstantial evidence places aromatic residues in the active site of a number of proteins that interact with cations but the presence of cation-π interaction in biological system does not rule out the conventional ion-pair interaction. In fact there is a good evidence for the existence of both type of interaction in model system.