Extended Data Fig. 7: Sequence and structural conservation analysis of GPCR-like folds (GLF).

a, Cartoon representation of a GLF colored by residue diversity of the in vitro validated folded designs. b, The sequence diversity of all GLF designs is visualized on a per-residue level in the plot, with a dotted line indicating the average sequence diversity across the structure. c, Sequence logo of residues in experimentally validated and folded GLF designs. The natural GLF contained a highly conserved DRY motif in the first intracellular loop (residues 26 to 28) and a PXXY motif (residues 225 to 227) in the seventh helix which are not present in our designs. All other positions depicted contained proline residues in the design target, which have a higher prevalence for some positions but are not required. d, Cartoon depiction of the crystal structure of GLF_18 colored by backbone RMSD_Cα per residue when compared against the target fold (left) and the design model (right), with individual values plotted in panel e. f, Depiction of the GLF_32 crystal structure colored by backbone RMSD_Cα, with individual values plotted per residue in panel g.