Intramolecular backbone...backbone hydrogen bonds in polypeptide conformations. The other way around: epsilon-turn

In this study, we performed a detailed literature survey of the epsilon-turns in peptides and their analysis on proteins. This 3D-structural feature is characterized by an eleven-membered pseudo-cycle closed by an intramolecular backbone...backbone H-bond. Interestingly, in this motif the direction of the N-H...O=C H-bond runs opposite to that of the much more popular and extensively investigated alpha-, beta-, and gamma-turns. We did not authenticate unequivocally this main-chain reversal topology in any linear short peptide. However, it is frequently observed in small cyclic peptides formed by four-, five-, and six amino acid residues with stringent geometric requirements. Rather surprisingly, epsilon-turns do occur in proteins, although to a relatively moderate extent, as an isolated feature or in the turn segment of hairpin motifs based on two antiparallel, pleated beta-strands. Moreover, the epsilon-turn may also host not only the seven-membered, intramolecularly H-bonded, pseudo-cycle termed gamma-turn, either of the classic or inverse type, but also one (or even two) cis peptide bond(s) or a beta-bulge conformation. Based on their phi,psi backbone torsion angles, we were able to classify the protein epsilon-turns in six different families. Preliminary conformational energy computations using the DFT methodology were also performed on the epsilon-turns adopted by the amino acid triplet -Gly-Gly-Gly- (Gly is the most commonly found residue at each of the three positions in our statistical analysis of proteins). Again, in this currently ongoing computational study, six families of turns were identified, most of them matching closely those extracted from our investigation on proteins.