Protein-protein interactions that are mediated by short linear motifs (SLiMs) in intrinsically disordered regions (IDRs) of proteins are notoriously difficult to study. Recently, pull-downs with synthetic peptides in combination with quantitative mass spectrometry emerged as a powerful screening approach. Here, we briefly highlight the relevance of SLiMs for protein-protein interactions, outline existing screening technologies, discuss unique advantages of peptide-based interaction screens, and provide practical suggestions for setting up such peptide-based screens.
