Design of Multi-Specificity in Protein Interfaces
Figure 6
Distribution of Optimization in Promiscuous Interfaces
Predicted per-residue binding score improvements (relative to native) for sequences selected in single-constraint (A) and multi-constraint (B) simulations. Coloring indicates the magnitude of predicted improvement over native. Darker-colored bars (compromise value 1–1.5, orange; more than 1.5, red) indicate positions for which the simulation predicts a non-native residue to bind stronger than native. Lighter-colored bars (compromise value 0–0.5, wheat; 0.5–1, yellow) indicate simulations recovered the native (or near-native) residue type. Whether optimization was in the context of single or multiple partners, positions calculated to be hotspots (see Methods) consistently returned the native amino acid as optimal (244/303 and 272/303, for single- and multi-constraint simulations, respectively). In contrast, roughly half of non-hotspot interface positions were predicted as suboptimal for binding when each partner was considered separately (350/682), but only a quarter (167/682) were estimated to still be suboptimal in the context of binding multiple partners. Overall, the total number of interface sites for which improvements in binding scores could be found was significantly less for multi-constraint optimizations. Scores for the same residue position with differing binding partners are included in all plots.