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 performed database and conformational searches, along with molecular dynamics simulations, to study two local interactions detected by 1H-NMR in tetrapeptides excised from bovine pancreatic trypsin inhibitor: aromatic-(i+2)amide and (i-1)cisproline-aromatic. For both types of interaction, at least two major and distinct peptide conformations are identified in the folded state. The aromatic-(i+2)amide interaction can have parallel and perpendicular arrangements of the N-H bond and the aromatic ring. The (i-1)cisproline-aromatic interaction can have close packing 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 interactions are weak, they may influence folding and binding properties. The combination of search and simulation techniques provides a useful route towards obtaining an atomic-detail description of peptides exhibiting these interactions.
Nardi
F
F
European Molecular Biology Laboratory, Heidelberg, Germany.
Worth
G A
GA
Wade
R C
RC
D000577:Amides / Q000737:chemistry; D007611:Aprotinin / Q000737:chemistry*; D016208:Databases, Factual; D009682:Magnetic Resonance Spectroscopy; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D012996:Solutions; D014867:Water / Q000737:chemistry
D000577:Amides; D010455:Peptides; D012996:Solutions; D014867:Water; D007611:Aprotinin