In order to elucidate the mechanisms of radical-initiated unfolding of a helix, the thermodynamic functions of hydrogen abstraction from the C-alpha, C-beta and amide nitrogen of Ala(3) in a homopeptapeptide (N-Ac-AAAAA-NH2; A5) by HO center dot, HO2 center dot, and O-2(-center dot) were computed using the B3LYP density functional. The thermodynamic functions, standard enthalpy (Delta H degrees), Gibbs free energy (Delta G degrees), and entropy (Delta S degrees), of the reactants and products of these reactions were computed with A5 in the 3(10)-helical (A5(Hel)) and fully extended (A5(Ext)) conformations at the B3LYP/6-31G(d) and B3LYP/6-311+G(d,p) levels of theory, both in the gas phase and using the C-PCM implicit water model. With quantum chemical calculations, we have shown that H abstraction is the most favorable at the C-alpha followed by the C-beta, then amide N in a model helix. The secondary structure has a strong influence on the bond dissociation energy of the H-C-alpha, but a negligible effect on the dissociation energy of the H-CH2 and H-N bonds. The HO center dot radical is the strongest hydrogen abstractor, followed by HO2 center dot and finally O-2(-center dot). More importantly, secondary structure elements, such as H-bonds in the 3(10)-helix, protect the peptide from radical attack by hindering the potential electron delocalization at the C-alpha when the peptide is in the extended conformation. We also show that he unfolding of the A5 peptide radicals have a significantly higher propensity to unfold than the closed shell A5 peptide and confirm that only the HO center dot can initiate the unfolding of A5(Hel) and the formation of A5(Ext)(center dot). By comparing the structures, energies, and thermodynamic functions of A5 and its radical derivatives, we have shown how free radicals can initiate the unfolding of helical structures to beta-sheets in the cellular condition known as oxidative stress.