Precise side-chain conformation analysis of l-phenylalanine in α-helical polypeptide by quantum-chemical calculation and 13C CP-MAS NMR measurement

To clarify the positive role of side-chain conformation in the stability of protein secondary structure (main-chain conformation), we successfully calculated the optimization structure of a well-defined α-helical octadecapeptide composed of l-alanine (Ala) and l-phenylalanine (Phe) residues, H–(Ala)8–Phe–(Ala)9–OH, based on the molecular orbital calculation with density functional theory (DFT/B3LYP/6-31G(d)). From the total energy and the precise secondary structural parameters such as main-chain dihedral angles and hydrogen-bond parameters of the optimized structure, we confirmed that the conformational stability of an α-helix is affected dominantly by the side-chain conformation (χ1) of the Phe residue in this system: model A (T form: around 180° of χ1) is most stable in α-helix and model B (G+ form: around −60° of χ1) is next stable, but model C (G− form: around 60° of χ1) is less stable. In addition, we demonstrate that the stable conformation of poly(l-phenylalanine) is an α-helix with the side-chain T form, by comparison of the carbonyl 13C chemical shift measured by 13C CP-MAS NMR and the calculated one.