Figure 1.

Distribution of protein–protein complexes generated by structural alignment with homologous templates. The i-RMSD is calculated relative to the native X-ray structure of the complex (thick line with circles), as well as to the generated structure with the largest i-RMSD from the native structure (thin line). The distinct minimum in the bimodal native-based distribution separates the main binding mode (smaller i-RMSD values) from the alternative binding modes (larger i-RMSD values). For comparison, the distribution from the alternative, most distant binding mode (the largest i-RMSD from the native structure) shows a similar to the native-based distribution pattern. A greater dispersion of values in this distribution corresponding to small i-RMSDs is likely caused by an overall smaller number of generated complexes (see text), and lower cluster occupancy at the putative alternative binding site, than at the native site.¹⁶ The qualitative similarity of the distributions, obtained from the different reference points, indicates similar separation of the binding modes.