LAUSR

Significance De novo design of mini-proteins for engineering new functions has primarily focused on all-alpha and alpha-beta folds. Despite the enormous functional diversity observed in naturally occurring beta barrels less than 70 residues in length, the de novo design of these structures has not been achieved. Here, we describe the de novo design and characterization of four different classes of small beta barrels. The results provide insight into the determinants of folding and design of this important class of proteins, and provide routes to the design of high-affinity binding proteins.