Folding Cooperativity of Synthetic Polypeptides with or without "Tertiary" Interactions.

Model-based studies on helix-coil transition and folding cooperativity of synthetic polypeptides have contributed to the understanding of protein folding and stability and to the development of polypeptide-based functional materials. Polypeptide-containing macromolecules with complex architectures, however, remain a challenge in the model-based analysis. Herein, a modified Schellman-Zimm-Bragg model has been utilized to quantitatively analyze the folding cooperativity of polypeptide-containing macromolecules. While the helix-coil transition of homopolypeptides (e.g., poly(ε-benzyloxycarbonyl-l-lysine) (PZLL)) can be described by the classic model, the folding of grafted polypeptide chains in the comb macromolecules (e.g., polynorbornene- g -poly(ε-benzyloxycarbonyl-l-lysine) (PN- g -PZLL)) cannot be accurately predicted by the existing theories, due to the side-chain interactions between grafted polypeptides in the comb macromolecules. Incorporating nonlocal interaction explicability into the statistical mechanics treatment is found to be instructive to account for the possible "tertiary" interactions of polypeptides in the macromolecules with complex architectures.