Modular pocket sequence redesign generates binders for peptide sequences that are not strictly repeating. Left, ribbon diagrams of base designs (rows 1 and 3) and versions with a matching subset of the protein and peptide modules redesigned. The ribbon diagrams show the cognate designed and redesigned assemblies; for example, the first row shows a six-repeat PLP binding design in complex with PLPx6, and the second row the same backbone with repeat units 3 and 4 redesigned to bind PEP instead of PLP, in complex with a PLP 2 PEP 2 PLP 2 peptide. The redesigned peptide and protein residues are shown in purple sticks and yellow, respectively. Right, orthogonality matrix. Biotinylated target peptides were loaded onto biosensors, and incubated with designed binders in solution at the indicated concentrations. Red rectangle boxes indicate cognate complexes. Octet signal was normalized by the maximum signal of the cognate designed binder–target pair.
