Defining Tertiary Structure with Designed Beta-Hairpins

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This proposal aims to increase our understanding of fundamental biomolecular recognition between protein secondary structures to determine the necessary requirements for high affinity, high specificity tertiary interactions. We will investigate interactions between naturally occurring sidechains as well as unnatural amino acids that we expect will provide higher stability or specificity. This research will provide important fundamental insights into the understanding of protein-protein interactions and will provide critical insight into requirements for disrupting protein-protein interactions. In addition, these studies will expand the set of molecular recognition scaffolds available for controlling molecular assembly and provide new systems to create well-defined supramolecular structures for a variety of applications in medicinal chemistry, de novo design, and materials chemistry.With regard to education, this research also has broad impact. Through hands-on research, discussion of the literature, interdisciplinary courses, interaction with seminar speakers in the field, and presentations at conferences, this research program will educate both graduate and undergraduate students in organic, biological, and biophysical chemistry, providing a strong interdisciplinary background which is necessary in the increasingly interdisciplinary scientific workforce