Abstract
<jats:p> The Negative Fragmentation Approach (NFA), incorporating counterpoise correction for basis-set superposition error (BSSE), enables site-specific evaluation of intra- and intermolecular interaction energies using quantum chemical calculations, even for covalently connected or embedded molecular sites. Here, we applied NFA to quantify BSSE-corrected hydrogen-bond (H-bond) interaction energies between the backbone carbonyl and amide groups in peptide models in various secondary structures: α-, π-, and 3 <jats:sub>10</jats:sub> -helices, and parallel and antiparallel β-sheets. The NFA-calculated H-bond energies in the whole second-structure peptide models were compared with those in the corresponding minimal H-bond (minHb) models composed of two separate Nmethylacetamide molecules, which isolate a single donor-acceptor H-bond from the other backbone groups. The differences between the whole and minHb models indicate conformation-dependent reduced or enhanced polarization of H-bond donor and acceptor groups by neighboring backbone polar groups. The NFA-derivd H-bond energies were also compared with those obtained using the AMBER classical force field. </jats:p>