(427a) Directed Evolution of Peptide Conformational Changes

Proteins and peptides are second only to water in cellular abundance and are involved in nearly every aspect of cellular function. The biochemical properties of these molecules have been widely studied, but their physical properties, particularly triggered changes in shape or conformation, have received less attention. Unfortunately, the difficulty in rapidly assessing conformational changes has hampered efforts to investigate and to re-engineer these molecules. Therefore, we are developing protein-based peptide conformational change sensors that will be used to macroscopically signal that a conformational change has occurred in an attached peptide sequence. These sensors will allow for the utilization of directed evolution techniques to evolve novel peptides that can respond to unique environmental stimuli, which will be useful for nanotechnology applications. And, the sensors will also permit the use of high-throughput screening to determine conditions that govern the folding of natural peptides implicated in the pathology of neurodegenerative diseases. Together, these approaches will enable us to gain a deeper understanding of the molecular underpinnings of the conformational behavior of peptides.