Extended Data Fig. 3: Diffusing de novo binder design to CP and disorder and secondary structure prediction for CP and VP48.
From: Diffusing protein binders to intrinsically disordered proteins
a, IUPred3 predictions for the CP, the predicted disorder scores remain above 0.5 across the targeted regions, indicating that CP is intrinsically disordered14,15. b, JPred4 (ref. 16) secondary structure predictions for CP, three residues within the target region show strand propensity (green arrows). c, Sequence-input diffusion was carried out, allowing CP to sample diverse conformations. Representative examples are shown here. The diverse conformations of CP and protein binder are rendered in blue and wheat colour, respectively. d, Design model of the initial hit CP-95 which was also the starting point of two-sided partial diffusion. e, The BLI data revealed that the binding affinity of the initial hit CP-95 is 16 μm. f, Scatter plot showing the distribution of designs based on the number of hydrogen bonds (hbond_number) and the RMSD of the binder (rmsd_binder). Each blue dot represents a design, while the red dot marks a validated hit. The dashed black lines indicate the cutoff values based on the initial hit criteria (hbond_number = 13 and rmsd_binder = 0.545). g and j, Circular dichroism data show that the binder CP-35 (g) and VP48-2 (j) have helical secondary structure and are stable up to 95 °C (inset). h, Jpred4 predictions for VP48, indicating VP48 doesn’t have secondary structure propensity. i, Predicted disorder profiles for VP48 generated by IUPred3 indicate low disorder propensity in its central segments. Combined with the low pLDDT scores predicted by AlphaFold (Fig. 1A), these results suggest that VP48 is structurally ambiguous.
