The previously proposed molecular tailoring approached (MTA) [Deshmukh, M. M.; Gadre, S. R.; Bartolotti, L. J. J. Phys. Chem. A 2006, 110, 12519] for the estimation of intramolecular O-H···O hydrogen bond energy is extended to that for the N-H···O-C bond within polypeptides. The methodology is initially tested on a tetrapeptide containing two types of N-H···O-C hydrogen bonds and is found to distinguish between them. The estimated values are in good agreement with the trends predicted by the geometrical parameters. Furthermore, this methodology is applied to partially as well as fully substituted, capped polyglycines that contain five glycine residues (acetyl-(gly) 5 -NH 2 ) to check the effect of substituents on the energetics of hydrogen bonds. The estimated N-H···O-C bond energy values lie in the range of 4-6 kcal/mol. These estimated values are not only in concurrence with the geometric parameters but also able to reflect the subtle effects of substituents for the substituted polypeptides studied in the present work.