The effects of H-bond cooperativity upon the secondary structures of peptides

Molecular orbital calculations show that amidic H-bonds within peptide structures can be extremely cooperative in some cases (a-helices), or not (coliagen-like triple helices), while in others (beta-sheets) cooperativity becomes masked by interactions that are weakened when new H-bonds are formed. There are cases where cooperativity is unimportant and H-bonding interactions can reasonably be approximated as being additive. In such cases, empirically derived pair-wise additive potentials might be expected to reproduce structures. However, those cases where cooperativity is important require more sophisticated analysis as the cooperative interactions between the individual H-bonds can become the dominant energetic driving force for the observed peptide structures. As in the case of many molecular crystals, pairwise additivity of the interactions of individual H-bonds can seriously underestimate the stability of the structure(s), leading to erroneous predicted structures.