Conformational Analysis of n→π* Interactions in Collagen Triple Helix Models

Ab initio calculations of three models of collagen at positions Pro–Pro–Gly (1), Pro–Gly–Pro (2), and Gly–Pro–Pro (3) were performed to assess the conformational variation of n→π* contributions to the stability of the collagen triple helix. Full conformational analyses by relaxed potential-energy scans of the Ψ dihedral angle of the central residue in models 1, 2, and 3 revealed the presence of several n→π* interactions. In model 2, with Gly as the central residue, both the Φ and Ψ dihedral angles of Gly were scanned. Most minima of each model contained one or two n→π* interactions, with pyramidalization at the π* carbon. We also observed pyramidalization at the n→π* donor amide nitrogens. Minima with hydrogen-bond or non-native n→π* interactions compete with the collagen stabilizing n→π* interactions. The collagen-like n→re-π* conformation was found as the global minimum only in model 3. The global minimum of 1 had a 5-membered ring hydrogen bond with an additional weak n→si-π* interaction. The global minimum of 2 was in the extended conformation. We predict that the n→π* interactions found in native collagen, while individually small, cumulatively contribute to the stability of the triple helix conformation of collagen.