Protein interactions range from ordered to disordered binding modes
(A) Structural order and contact patterns of the bound complex. In ordered binding modes, represented by the complex of p53 tumor suppressor (blue) with Mdm2 (gray, PDB: 2MWY, [12]), the binding interface is well-defined, the bound conformations exhibit limited mobility. Ordered binding modes are characterized by a well-defined contact pattern between specific residues. In disordered binding modes, represented by the complex formed between Gcn4 transcription factor (orange) and Med15 (gray, PDB: 2LPB [18]), the binding interface is conformationally heterogeneous as either or both partners are disordered in the bound complex. Disordered binding modes are generated by alternative contact patterns among the same set of residues. In context-dependent binding modes, represented by the complex formed between p53 (green) and HMGB1 (gray, PDB: 2LY4, [11]) the degrees of disorder are modulated by the cellular or experimental conditions. In context-dependent binding modes, some contacts are well-defined, whereas others are variable and depend on the conditions. The upper panels show the structure of the bound complex, while the lower panels display the residues, which are in contact in at least one model of the ensemble. (B) Heterogeneity of contact patterns. The variability of interactions can be quantified by the contact frequency, defined as the fraction of models in which the given residue is observed to form a contact (defined by https://getcontacts.github.io). The color scale ranges from more stable (blue) to more transient (light orange) interactions corresponding to highly or sparsely populated contacts. The interface residues of p53 exhibit more stable, well-defined contacts in complex with Mdm2, while more variable contacts with HMGB1. In contrast, Gcn4 forms contacts through any of its residues with a low frequency, leading to contact pattern variability and disordered binding modes.