Fig. 2: Generalization of model design to unseen topologies.

Data are presented as mean values ± 95% CI or as box plots with a median center, bounds of boxes corresponding to interquartile range (IQR), whisker length 1.5*IQR, and outliers rendered outside of this range. A The trained model is used to either repack rotamers or design entirely new sequences onto unseen test set structures with non-train-set CATH topologies. B, C Model-guided rotamer recovery for native test cases. B Rotamer repacking accuracy for buried core residues versus solvent-exposed residues as a function of degree cutoff. C 5 models superimposed with side chains shown as black lines compared to the native conformation shown in purple outline for test case 3mx7. D–H Performance of sequence design onto test case backbones. D Native sequence recovery rate across 50 designs for all residues vs. buried core residues. E Position-wise amino-acid distributions for test case 1cc8. Columns are normalized. (Top) Native sequence and aligned homologous sequences from MSA (n = 670). (Bottom) Model designs (n = 50). F Cross-entropy of Psipred secondary structure prediction from a sequence with respect to DSSP assignments^{54,65,66,67,68,76}. G Fraction occurrence of glycines at positive ϕ backbone positions across test cases. H Fraction occurrence of N-terminal helical capping residues across designs for test cases with capping positions. I, J Far UV circular dichroism (CD) spectroscopy data for selected test case designs. I Mean residue ellipticity Θ_MRW (10³ deg cm² dmol⁻¹) for CD wavelength scans at 20 °C for native structures (blue, dashed) vs. select model designs (orange, solid) 1acf d3, 1bkr d2, 1cc8 d2, and 3mx7 d4. Sequence identity to native reported within each panel. J Thermal melting curves for select model designs monitoring θ_MRW (10³ deg cm² dmol⁻¹) at 222 nm or 217 nm for 3mx7.