| 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 beta-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 bcapping strategies, an extensive residue search of [4:6] b-turns and a system to examine long flexible loops (> 20 residues), in which the loop connects beta-strands that are in excess of 80% in a folded state. Lastly a conformational pH switch was developed, controlling the folded state of bsheets. With these improvements, beta-sheet design can become quite routine, hopefully expanding the usefulness of these ubiquitous structures. |
