The interaction between the aromatic ring of an amino acid and the α-helical polypeptide backbone was investigated by studying the conformation of α-helical Ala-based model peptides, with Tyr replacement in the N-terminaland inner helical positions, using 'H NMR, molecular dynamics (MD) simulations, and a protein database search. NOE cross-peaks between the hydrogens of the aromatic ring at position i and the hydrogen of the backbone amide in positions i, i+1, i+3 and i+4 indicated the proximity of the aromatic ring to the backbone. Interaction between the aromatic ring and the backbone seemed to be highly dependent on the orientation of the aromatic side chain to the helical backbone because aromatic-backbone amide, aromatic-carbonyl, and aromatic-HCα interactions were observed in MD. Solvent screening by the aromatic side chain decreased the solvent accessible surface area of some polar backbone groups by more than 80%. These results indicate that aromatic-backbone interactions commonly occur in helical structures in proteins.