Quantum chemical studies on hydrogen bonds in helical secondary structures

We present a brief review of our recent computational studies of hydrogen bonds (H-bonds) in helical secondary structures of proteins, α-helix and 3(10)-helix, using a Negative Fragmentation Approach with density functional theory. We found that the depolarized electronic structures of the carbonyl oxygen of the ith residue and the amide hydrogen of the (i + 4)th residue cause weaker H-bond in an α-helix than in an isolated H-bond. Our calculations showed that the H-bond energies in the 3(10)-helix were also weaker than those of the isolated H-bonds. In the 3(10)-helices, the adjacent N–H group at the (i + 1)th residue was closer to the C=O group of the H-bond pair than the adjacent C=O group in the 3(10)-helices, whereas the adjacent C=O group at the (i + 1)th residue was close to the H-bond acceptor in α-helices. Therefore, the destabilization of the H-bond is attributed to the depolarization caused by the adjacent residue of the helical backbone connecting the H-bond donor and acceptor. The differences in the change in electron density revealed that such depolarizations were caused by the local electronic interactions in their neighborhood inside the helical structure and redistributed the electron density. We also present the improvements in the force field of classical molecular simulation, based on our findings. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12551-022-01034-5.