Fig. 2: Designed solenoid protein novelty and diversity.

A Natural and novel solenoid protein representation space structural similarity quantified by MDS of solenoid pairwise structural similarities. The solenoids produced by the in silico evolution loop are seen in color. Natural solenoid proteins are in grey and previous designed proteins in the PDB are grey with a black outline. Left-handed β-solenoids are outlined. B For each solenoid design, we identified the most similar structure in the PDB. Shown here are the least similar of these best matches, the alignments with the lowest TM-scores, for each solenoid type. These represent the most structurally novel designs. The lowest best-match TM-scores were: α-solenoids, 0.40 (PDB:2O8P); αβ-solenoids, 0.45 (PDB:4I6K); β-solenoids, 0.54 (PDB:1K8F). C Histograms showing the TM-score of the most similar structure in the PDB to the solenoid backbone designs for α-solenoids, αβ-solenoids and β-solenoids. Median TM-scores (dotted line) for the α-, αβ- and β-solenoids are 0.55, 0.59 and 0.62, respectively. D Histograms showing the E-value distribution for the closest hit in the non-redundant database for ProteinMPNN re-designed sequences, based on backbones generated from the in silico evolution loop for α-solenoids, αβ-solenoids, and β-solenoids. Only sequences with an RMSD < 5 Å compared to the original backbone after AF2 prediction, and a pLDDT >80, are included. The median E-values (dotted line) for the α-, αβ-, and β-solenoids are 1.44, 2.92 × 10⁻³, and 2.13 × 10⁻⁴, respectively.