Caps - Turns - Loops: Designing Better β-Hairpins

Abstract

As protein engineering promises advances in almost every field of science and medicine, a greater understanding of the protein folding problem is necessary to make these innovations a reality. This thesis examines one type of folded structure, the β-sheet. By designing several new peptide systems, the thermodynamics and kinetics of folding were examined quite thoroughly. Some of these include; a disulfide dimer “turnless” system used to investigate different β-capping strategies, an extensive residue search of [4:6] β-turns and a system to examine long flexible loops (> 20 residues), in which the loop connects β-strands that are in excess of 80% in a folded state. Lastly a conformational pH switch was developed, controlling the folded state of β-sheets. With these improvements, β-sheet design can become quite routine, hopefully expanding the usefulness of these ubiquitous structures.