Comparative Study of the Mechanical Unfolding Pathways of α- and β‑Peptides

Abstract

Using molecular simulations, we analyze the unfolding pathways of various peptides. We compare the mechanical unfolding of a β-alanine’s octamer (β-HAla₈) and an α-alanine’s decamer (α-Ala₁₀). Using force-probe molecular-dynamics simulations, to induce unfolding, we show that the 3₁₄-helix formed by β-HAla₈ is mechanically more stable than the α-helix formed by α-Ala₁₀, although both structures are stabilized by six hydrogen bonds. Additionally, computations of the potential of mean force validate this result and show that also the thermal stability of the 3₁₄-helix is higher. It is demonstrated that β-HAla₈ unfolds in a two-step fashion with a stable intermediate. This is contrasted with the known single-step scenario of the unfolding of α-Ala₁₀. Furthermore, we present a study of the chain-length dependence of the mechanical unfolding pathway of the 3₁₄-helix. The calculation of the dynamic strength for oligomers with chain lengths ranging from 6 to 18 monomers shows that the unfolding pathway of helices with an integer and noninteger number of turns has <i>m</i> + 1 and <i>m</i> energy barriers, respectively, with <i>m</i> being the number of complete turns. The additional barrier for helices with an integer number of turns is shown to be related to the breaking of the N-terminus’ hydrogen bond