Thermal decomposition of endothermic peaks during coil-to-helix transitions using the Zipper model

Abstract

Helix-coil transitions in biopolymers produce characteristic endothermic peaks in differential scanning calorimetry (DSC) whose shape represents thermodynamic stability. We present an analysis that fits the Zipper model to DSC endothermic peak data to extract four physically interpretable parameters: the melting temperature T_m, the helix formation enthalpy ΔH_u, the nucleation parameter σ, and the cooperative chain length N. The model is connected to DSC observables through the propagation parameter s(T) and the relation C_p^ex = −ΔH_cal · df_H/dT. The model is validated on three synthetic DSC datasets spanning distinct cooperativity regimes. T_m is recovered to within 0.1−2.5% across all cooperativity regimes. Recovery of ΔH_u, σ, and N degrades toward the weakly cooperative limit due to structural non-identifiability of the objective function.