The contribution of intrinsic disorder prediction to the elucidation of protein function

Current knowledge of protein function stems primarily from the detailed characterization of some protein domain families and from extensive homology-based annotation transfers. Intrinsically disordered proteins exploit complementary molecular recognition mechanisms and their study has potential to make a significant contribution to the field. Building on established computational biology techniques, efforts are now aimed at unveiling their biological roles at the molecular and system level. Recent developments towards identifying functional sites in disordered regions, and analysing how the occurrence of protein disorder in a gene can provide insight into its biochemical and cellular function are discussed.

► Protein disorder can be predicted from sequence with fairly high accuracy. ► Disorder predictions can help classify functional residues and infer gene function. ► Residues involved in disorder-related protein–protein interaction can be predicted. ► Conformational ensemble modelling may help probe disorder-related function. ► Disordered alternatively spliced genes may be important in development and disease.