LOCAL INTERACTIONS OF AROMATIC RESIDUES IN SHORT PEPTIDES IN AQUEOUS-SOLUTION - A COMBINED DATABASE AND ENERGETIC ANALYSIS

Although short peptides are usually structurally disordered in aqueous solution, particular peptide sequences display local structure. We pe rformed database and conformational searches, along with molecular dyn amics simulations, to study two local interactions detected by H-1-NMR in tetrapeptides excised from bovine pancreatic trypsin inhibitor: ar omatic-(i+2)amide and (i-1)cisproline-aromatic. For both types of inte raction, at least two major and distinct peptide conformations are ide ntified in the folded state. The aromatic-(i+2)amide interaction can h ave parallel and perpendicular arrangements of the N-H bond and the ar omatic ring. The (i-1)cisproline-aromatic interaction can have close p acking of the aromatic ring to the (i-2)C alpha H or the (i-1)C gamma H but not both simultaneously. Although these local aromatic interacti ons are weak, they may influence folding and binding properties. The c ombination of search and simulation techniques provides a useful route towards obtaining an atomic detail description of peptides exhibiting these interactions.