Prediction of Protein-protein Interaction Sites in Intrinsically Disordered Proteins

Intrinsically disordered proteins (IDPs) participate in many biological processes by interacting with other proteins, including the regulation of transcription, translation, and the cell cycle. With the increasing amount of disorder sequence data available, it is thus crucial to identify the IDP binding sites for functional annotation of these proteins. Over the decades, many computational approaches have been developed to predict protein-protein binding sites of IDP (IDP-PPIS) based on protein sequence information. Moreover, there are new IDP-PPIS predictors developed every year with the rapid development of artificial intelligence. It is thus necessary to provide an up-to-date overview of these methods in this field. In this paper, we collected 30 representative predictors published recently and summarized the databases, features and algorithms. We described the procedure how the features were generated based on public data and used for the prediction of IDP-PPIS, along with the methods to generate the feature representations. All the predictors were divided into three categories: scoring functions, machine learning-based prediction, and consensus approaches. For each category, we described the details of algorithms and their performances. Hopefully, our manuscript will not only provide a full picture of the status quo of IDP binding prediction, but also a guide for selecting different methods. More importantly, it will shed light on the inspirations for future development trends and principles.