Protein folding and structure prediction: biological and physical perspectives

Thesis

Protein folding is poorly understood and distinct from protein structure prediction, encompassing the translation and folding process of proteins in vivo and in vitro. In this thesis, we examine the protein folding process from several perspectives. First, we implement models of the spatial constraints that the ribosome introduces in the protein folding process. We are unable to show that these constraints have a particular effect on the formation of protein structure. However, we identify and describe a method which improves protein structure prediction in SAINT2 by avoiding the disruptive effects of certain extension protocols. Then, we study the relationship between protein structure and the coevolutionary constraints under which the structure has evolved. We identify several relationships between the structure of the protein and the coevolutionary constraints that are found in the protein. We further compare contact prediction methods and show that different contact prediction methods identify different types of amino-acid contacts. Finally, we investigate obligate cotranslational protein folding in the E. coli proteome. We find a relationship between the behaviour of several folding analysis methods and the necessity of cotranslational folding for our proteins.

Authors: Chonofsky, MA

• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: Protein folding; Mutual information; Cotranslation; Coevolution
• Subjects: Biochemistry; Structural biology; Statistics