Computational Study of Conformational Changes in Intrinsically Disordered Regions During Protein-Protein Complex Formation

Intrinsically Disordered Regions (IDRs) even though they cannot form a defined three-dimensional structure play a pivotal role in modulating cellular processes and signalling pathways. In the present study, we analyse the conformational changes in IDRs upon complex formation using a non-redundant dataset of binary, X-ray solved 356 protein-protein (P-P) complexes and their corresponding unbound forms. IDRs are prevalent in both unbound and complex proteins and after comparing them in both groups they were categorised into three classes: (a) Disordered-Ordered (D-O), where IDRs present in first group were observed to be ordered in the second group (b) Disordered-Partial Ordered (D-PO), where IDRs present in the first group were found to be partially ordered in the second group and (c) Disordered-Disordered (D-D), where IDRs present in one group remained disordered in the other group. The study of secondary structures of residues in the D-O category reveals that majority of IDRs upon complexation form coils followed by helices and strands. Though majority of residues of IDRs in the D-O class are located at the surface of P-P complexes, we observe a significant number of residues form the interface suggesting that they contribute to the stability of the complexes. Amino acids of IDRs under the D-O category are also involved in polar interactions making hydrogen bonds with other residues as well as water. There are some structured and partially structured regions in the unbound proteins which upon complexation become completely disordered. These findings provide fundamental insights into the underlying principles of molecular recognition by disordered regions in P-P complexes.