Partition Function Zeros and Heat Capacity Decomposition Reveal HP Protein Foldability

The heat capacity decomposition method, a well-established analytical approach in polymer thermodynamics for elucidating thermal transitions in homogeneous polymers, is extended here to heterogeneous systems. We demonstrate that the decomposition of heat capacity based on partition function zeros allows the identification of transition-like crossovers originating from compact low-energy states, thereby enabling the evaluation of the foldability of HP sequences. The occurrence of significant crossovers between the collapse and folding transitions indicates slow folding behavior, whereas their absence characterizes good folders. This criterion is further validated through kinetic Monte Carlo simulations of two representative sequences.