The Effects of H-Bond Cooperativity upon the Secondary Structures of Peptides

Abstract

Molecular orbital calculations show that amidic H‐bonds within peptide structures can be extremely cooperative in some cases (α‐helices), or not (collagen‐like triple helices), while in others (β‐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.