Relative strengths of NH..O and CH..O hydrogen bonds between polypeptide chain segments

Correlated ab initio calculations are used to compare the energetics when the CH and NH groups of the model dipeptide CHONHCH2CONH2 are each allowed to form a H-bond with the proton acceptor O of a peptide group. When the dipeptide is in its C7 conformation, the NH..O H-bond energy is found to be 7.4 kcal/mol, as compared to only 2.8 kcal/mol for the CH..O interaction. On the other hand, the situation reverses, and the CH..O H-bond becomes stronger than NH..O, when the dipeptide adopts a C5 structure. This reversal is important as C5 is nearly equal in stability to C7 for the dipeptide, and is representative of the commonly observed beta-sheet structure in a protein. Immersing the dipeptide-peptide pair in a model solvent weakens both sorts of H-bonds, and in a fairly uniform manner. Consequently, the trends observed in the in vacuo situation retain their validity in either aqueous solution or the protein interior. Likewise, the desolvation penalty, suffered by removing a H-bonded complex from water and placing it in the less polar interior of a protein, is quite similar for the NH..O and CH..O bonds.