Predicting Protein–Protein Interfaces that Bind Intrinsically Disordered Protein Regions

Publication date: Available online 15 June 2019Source: Journal of Molecular BiologyAuthor(s): Eric T.C. Wong, Jörg GsponerAbstractA long-standing goal in biology is the complete annotation of function and structure on all protein–protein interactions, a large fraction of which is mediated by intrinsically disordered protein regions (IDRs). However, our knowledge base of experimentally derived structures of such protein complexes is disproportionately small, partly due to challenges in studying interactions of IDRs. Here, we introduce IDRBind, a computational method that by combining gradient boosted trees and conditional random field models predicts binding sites of IDRs with performance approaching state-of-the-art globular interface predictions, making it suitable for proteome-wide applications. Although designed and trained with a focus on molecular recognition features (MoRFs), which are long interaction-mediating-elements in IDRs, IDRBind also predicts the binding sites of short peptides more accurately than existing specialized predictors. Consistent with IDRBind's specificity, a comparison of protein interface categories uncovered uniform trends in multiple physicochemical properties, positioning MoRF interfaces between peptide and globular interfaces.Graphical abstract

Source: Journal of Molecular Biology - June 15, 2019 Category: Molecular Biology Source Type: research