Structural investigations of peptide folding and unfolding in solution

Thesis

Proteins are the essential biological working molecules in all living beings. Their function depends on their ability to adopt a specific three-dimensional structure in aqueous solution. The mechanism of this folding process, and conversely the loss of protein structure, unfolding, is still not well understood, especially on the atomic scale where these interactions occur in vivo. In this thesis, the structures of small model peptides have been investigated in aqueous solutions in order to understand how water, urea and other co-solutes influence protein folding and unfolding. Using a combination of neutron diffraction enhanced by isotopic substitution and computer simulations, it was found that urea, generally at any probed concentration, decreases ionic interactions with the peptides in solution. When the peptide backbone is solvent accessible, urea interacts directly with the polar peptide backbone and replaces water molecules at higher urea concentrations. Further, the results indicate an ambiguous in uence of water on peptide folding vs. conformational stability. The formation of β-turn like structures, and possibly intra-peptide hydrogen bonds in general, appears to be dependent on a specific backbone hydration pattern, facilitated by the local amino acid sequence. Conversely, hydrophobic residues in folded protein structures are particularly sensitive, in terms of conformation and hydration, towards an increased peptide backbone hydration.

Authors: Steinke, N

• DOI: 10.5287/ora-r5qax2bek
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford