Abstract Protein folding represents a fundamental biophysical process that determines cellular functionality and organismal viability. The stability of folded protein conformations is highly sensitive to environmental perturbations, particularly thermal fluctuations and oxidative stress. These stressors can induce partial unfolding, misfolding, aggregation, or irreversible structural damage, ultimately contributing to pathological states and cellular dysfunction. This study investigates the biophysical mechanisms underlying protein folding stability under combined thermal and oxidative stress conditions. Emphasis is placed on conformational flexibility, intramolecular bonding networks, solvent interactions, and redox-sensitive amino acid residues. Experimental findings from spectroscopic, calorimetric, and fluorescence-based structural analyses are integrated with theoretical models of folding landscapes. The research examines stress-induced conformational transitions in representative globular proteins and evaluates how structural resilience depends on secondary structure composition, hydrophobic core organization, and disulfide bond integrity. Particular attention is given to oxidative modification of cysteine and methionine residues and its impact on tertiary structure stability. The results provide an integrative biophysical framework for understanding how proteins maintain structural integrity under stress and how destabilization pathways may be mitigated in biological systems.
Min et al. (Tue,) studied this question.