Protein–protein interactions (PPIs), often mediated by short linear motifs (SLiMs), shape cellular functions. This review provides an overview of SLiMs, and scrutinises current PPI detection techniques, highlighting their relevance to SLiM-mediated interactions and addressing challenges in detecting domain–motif interactions (DMIs). Case studies, like BioGrid database analysis, suggest high-throughput PPI methods as reliable sources for predicting DMIs, enriching our understanding of cellular dynamics.

Protein–protein interactions (PPIs) are often mediated by short linear motifs (SLiMs) in one protein and domain in another, known as domain–motif interactions (DMIs). During the past decade, SLiMs have been studied to find their role in cellular functions such as post-translational modifications, regulatory processes, protein scaffolding, cell cycle progression, cell adhesion, cell signalling and substrate selection for proteasomal degradation. This review provides a comprehensive overview of the current PPI detection techniques and resources, focusing on their relevance to capturing interactions mediated by SLiMs. We also address the challenges associated with capturing DMIs. Moreover, a case study analysing the BioGrid database as a source of DMI prediction revealed significant known DMI enrichment in different PPI detection methods. Overall, it can be said that current high-throughput PPI detection methods can be a reliable source for predicting DMIs.