Abstract: De novo designed proteins with binding activity are disclosed, which were designed starting from a desired functional site and jointly filling in the missing sequence and structure needed to complete the protein, and uses of the binding proteins.

Abstract: Polypeptide are disclosed that comprise an amino acid sequence at least 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence selected from the group consisting of SEQ ID NO:1-1615, not including any functional domains added fused to the protein (whether N-terminal, C-terminal, or internal), and wherein the 1, 2, 3, 4, or 5 N-terminal and/or C-terminal amino acid residues may be present or absent when considering the percent identity.