Fig. 2.

trRosetta predicts properties of the folding energy landscape. (A) trRosetta better predicts which designs will have high Boltzmann probabilities than Rosetta-based energy calculations, which only see the target conformation (classifications for P_near > 0.8, AUC_trRosetta = 0.81 vs. AUC_Rosetta = 0.65, n = 4,204 designs). (B) trRosetta correctly predicts dilution of probability for designs with multiple low-energy conformations (columns 2 to 4) compared with designs with a single global energy minimum (column 1). Structural decoys were binned, and the mean trRosetta score corrected for background $\left(-\text{log}{P}_c\left(struct.|seq.\right)\right)$ is represented by the color gradient from dark blue (high probability) to red (low probability). (C) Structures of the lowest-energy representatives (indicated by circles on the energy landscape). The designed structures and alternative states are shown on the left and right, respectively, of each column. (D) Selected examples of probability distributions (Cβ–Cβ distance prediction) for specific i,j pairs (numbering indicated on the top) demonstrating bimodality. The actual distances observed in the designed and alternative structures are indicated by vertical lines (blue and red, respectively) and shown as spheres on the corresponding structures. More examples are shown in SI Appendix, Fig. S4, and an analysis of the prediction of bimodality from distributions of individual i,j pairs can be found in SI Appendix, Fig. S5.