Predominant torsional forms adopted by oligopeptide conformers in solution: parameters for molecular recognition.

In this paper, we describe the predominant conformational forms adopted by tripeptides and higher oligopeptides in aqueous solution. About 50 tripeptides and almost 20 higher oligopeptides (4-6 residues) were subjected to conformational analysis using SYBYL Random Search. As with dipeptides (Grail BM, Payne JW. J. Peptide Sci. 2000; 6: 186-199), both tripeptides and higher oligopeptides were found to occupy relatively few combinations of psi-phi space that were distinct from those associated with predominant protein secondary structures (e.g. helices and beta-sheets). Again, the preferred psi (psi) values for the first residue (i - 1) were in sectors encompassed by the ranges from +150 degrees to +/-180 degrees, +60 degrees to +90 degrees and -60 degrees to -90 degrees, which were combined with preferred phi (phi) values for the second residue (i) in sectors with ranges from -150 degrees to +/-180 degrees, -60 degrees to -90 degrees and +30 degrees to +60 degrees. It was notable that tripeptides and, to a greater extent, higher oligopeptides adopted an initial psi (psi) (Tor2) from +150 degrees to +/-180 degrees. For tripeptides, their N-C distances (distance between N-terminal nitrogen and C-terminal carbon atoms) distribute about 6.5 A to give shorter, 'folded' conformers that are similar in length to dipeptides, and longer, 'extended' conformers that are distinct. Furthermore, for higher oligopeptides, their N-C distances did not increment in relation to their increasing number of residues and short, 'folded' conformers were still present. These findings have a bearing upon the recognition of these molecules as substrates for widely distributed peptidases and peptide transporters.