Energetics of intrachain salt-linkage formation in collagen.

The energy of formation of salt linkages between Arg or Lys with Asp or Glu in a polypeptide chain having the collagen fold have been estimated using the fully empirical energy minimization scheme AMBER. The polypeptide was considered both in an isolated and a hydrated triple helical state. The collagen fold associated with a one-bonded triple helical conformation allows intrachain salt linkages having stabilization energies of 60-100 kcal when the reacting residues are separated by no more than two intervening residues. The amino end of one side chain always approaches the carboxyl end of the other side chain, and simultaneously approaches the carbonyl oxygen of the intervening backbone residue. The salt linkage conformation and the backbone conformation of the isolated collagen fold in vacuo are maintained when the molecules are in a hydrated triple helix. These results are compatible with a fold-forming role for salt linkages, especially in proline poor regions, during collagen polypeptide synthesis, and with the persistence of intrachain salt linkages throughout molecular and fibril assembly.