THE AROMATIC-(I+2) AMINE INTERACTION IN PEPTIDES

The interaction between an aromatic ring and an amine group has been p roposed to be important for the behavior of proteins and peptides. A s pecial case, notable in the folding pathway of BPTI, is the interactio n of the aromatic side chain of the ith residue with the amine group i n the peptide link to the (i+2) th residue. In this paper, molecular m echanics calculations, employing the CHARMm22 force field together wit h a simple model of a hydrogen bonding environment, are used to system atically search torsion space to find the favorable conformations for tripeptides containing this interaction as defined by the NMR ring shi ft on the amine proton. When all hydrogen-bonding atoms in the peptide are assumed to be able to make hydrogen bonds to solvent molecules, a ll favored conformers found have the amine group lying approximately p arallel to the aromatic ring. In this geometry, the aromatic-amine int eraction energy is dominated by the interaction energy of the (i+2) am ine group with solvent and the rest of the (i+2)th residue with the ar omatic ring. When a solvent hydrogen-bond acceptor is not available fo r the (i+2) amine proton, most of the favorable conformers have the am ine group perpendicular to the ring. This geometry is known to be the minimum energy geometry for the isolated aromatic-amine interaction. F or steric reasons, the majority of minimum energy conformers on the tw o potential energy surfaces are favorable for glycine-rich tripeptides . The geometries and sequence selectivities of the minimum energy conf ormers are found to fit the distribution observed in a set of tripepti des containing this interaction extracted from a database of 297 repre sentative protein crystal structures.