Fig. 3. Localization of the residues responsible for the correlations in apo and holo forms of the PDZ domain.

Core residues responsible for the two-state correlations of the apo state (a, b) are localized around the ligand-binding site and the protein’s hydrophobic core, whereas core residues responsible for the two-state correlations of the PDZ2 RA-GEF2 complex (c, d) are localized to the other side of the protein β-sheet. The 15 highest correlated residues, as determined by the correlation matrices shown in Fig. 2c, f are highlighted as a single volume entity on the two-state PDZ2 structures including state-dependent ribbon coloring and sidechain representation. As it is visible from the protein 3D structure, the highest correlations are concentrated in the protein binding site and all sites involved in the conformational selection mechanism shown in Figs. 4, 5.