Hydrogen bond donors and acceptors are generally depolarized in α-helices as revealed by a molecular tailoring approach.

Hydrogen-bond (H-bond) interaction energies in α-helices of short alanine peptides were systematically examined by precise density functional theory calculations, followed by a molecular tailoring approach. The contribution of each H-bond interaction in α-helices was estimated in detail from the entire conformation energies, and the results were compared with those in the minimal H-bond models, in which only H-bond donors and acceptors exist with the capping methyl groups. The former interaction energies were always significantly weaker than the latter energies, when the same geometries of the H-bond donors and acceptors were applied. The chemical origin of this phenomenon was investigated by analyzing the differences among the electronic structures of the local peptide backbones of the α-helices and those of the minimal H-bond models. Consequently, we found that the reduced H-bond energy originated from the depolarizations of both the H-bond donor and acceptor groups, due to the repulsive interactions with the neighboring polar peptide groups in the α-helix backbone. The classical force fields provide similar H-bond energies to those in the minimal H-bond models, which ignore the current depolarization effect, and thus they overestimate the actual H-bond energies in α-helices. © 2019 The Authors. Journal of Computational Chemistry published by Wiley Periodicals, Inc.