Date of Completion


Embargo Period



Cooperative folding, Polypeptide, Helix-Coil transition

Major Advisor

Yao Lin

Associate Advisor

Mu-Ping Nieh

Associate Advisor

Elena E. Dormidontova

Associate Advisor

Douglas H. Adamson

Associate Advisor

Fatma Selampinar

Field of Study



Doctor of Philosophy

Open Access

Campus Access


Using synthetic polypeptides as a model system, the theories of helix-coil transition were developed into one of the most beautiful and fruitful subjects in macromolecular science. Understanding the folding behaviors of polypeptides are critical for the rational design of polypeptide based systems and the comprehension of protein folding which is vital in achieving many biological functionalities. The classic models proposed by Schellman and Zimm-Bragg more than 50 years ago, differ in the assumption on whether the configuration of multiple helical sequences separated by random coil sections is allowed or not in a longer polypeptide chain. Zimm also calculated the critical chain lengths that facilitate such interrupted helices. The experimental validation of the prediction, however, was not carefully examined at that time, partially due to the difficulty in making longer polypeptides with narrow molecular weight distribution. Surprisingly, not many comprehensive studies about the folding of polypeptides were conducted in the past 50 years. Here, this dissertation work will present a step by step approach to understand the folding behaviors of polypeptide containing macromolecules. First, a semi-quantitative method was developed to understand the folding behavior of linear polypeptide and polypeptide grafted comb like polymers. It is found that the method is able to predict the length of the contiguous hydrogen bond network or helical sequence of linear polypeptide while fails to explain the folding behavior of the polypeptide side chain in the comb like architectures and the deviation of the folding behavior is caused by the side chain interactions due to the congested local environment. Second, we systematically examine the helix-coil transition and folding cooperativity of linear polypeptide using the quantitative model method. We find that for longer chains, polypeptides do exist as interrupted helices with scattered coil sections even in helicogenic solvent conditions, as predicted in Zimm-Bragg’s model. The critical chain lengths that facilitate such interrupted helices, however, are substantially smaller than Zimm’s original estimation. In addition, we find there might exist intramolecular interactions between different sections of the interrupted helices in the longer chains. Then we started to investigate the folding behavior of polypeptides in more complex architectures. We modified Zimm-Bragg model to study folding behavior of polypeptide contain macromolecules induced by temperature and solvent simultaneously. While the helix-coil transition of linear polypeptides can be described by the model, the folding of grafted polypeptide chains in the comb macromolecules cannot be accurately predicted by the existing theories, due to the complicated side chain interactions between grafted polypeptides in the comb macromolecules. New statistical mechanics treatment needs to consider the possible “tertiary” interactions of polypeptides in these complex architectures. In the end, the bulk properties and morphologies of polypeptide based fibers/films were preliminarily explored to understand the intra- and inter-molecular interaction without the solvent interaction.