THE DESIGN OF PROTEINS WITH NOVEL STRUCTURES AND ACTIVITIES. Lynne Regan, Dept. of Molecular Biophysics & Biochemistry, Yale University 266 Whitney Ave. New Haven, CT 06520

The research the I will discuss falls into three broad areas: helix-helix packing, the stabilization and design of beta sheet structure and the design and characterization of novel metal-binding sites in proteins.

Our work on helix-helix packing seeks to systematically vary the inter-helical residues in the four helix bundle protein, Rop. We aim to determine how structure and stability change as we repack the hydrophobic core of the protein. Of particular interest is to achieve an understanding of the "non-native" behavior that results from certain repacked cores. Similarly, our work on inter-helical loop connections seeks to determine how the structure and properties of a protein change as the length and topology of inter-helical loop connections is varied.

Our wrok on beta sheets seeks to understand both the intrinsic and pair-wise contributions of the amino acids to beta sheet stability.

Finally, we are involved in the design and characterization of novel metal binding sites in proteins. The focus of our studies is the design of tetrahedrally coordinated Zn(II) sites. To date we have introduced several such sites onto small protein frameworks. Our current research involves a detailed characterization of these sites to achieve a better understanding of what constitutes a successful design and thew modification of existing designs such that they have the potential to be catalytically active.