How did Linus Pauling explain protein denaturation?

In 1936, Linus Pauling and biochemist Alfred Mirsky published a foundational paper on protein structure that provided a clear explanation for the process of denaturation.1

They proposed that protein molecules naturally coil into specific, organized configurations to maintain their functional state. Denaturation occurs when these specific configurations are disrupted; essentially, the protein "uncoils" and assumes a random, disordered form because certain weak bonds holding the structure together are broken.1

This work was significant because it identified that the biological activity of a protein is tied to its specific structural folding, and that the loss of this structure—denaturation—results from the disruption of the internal linkages that maintain that native state.1