Chapter 6 - Modeling protein-protein interactions with intrinsically disordered proteins

Abstract

Intrinsically disordered proteins (IDPs) are abundant in proteomes, especially in eukaryotes. Protein-protein interactions (PPIs) involving an IDP are major players in the PPI network, comprising an estimated 15%–45% of all interactions. These disordered PPIs are prevalent in various important cellular processes and are associated with allosteric regulation, posttranslational modification, and alternative splicing. While IDPs lack a stable tertiary structure in isolation, they often become ordered when binding to a stable partner. The tertiary structure of the complex provides a molecular basis for understanding those pathways and related phenomena. Because capturing the IDP structures through experiments is difficult, computational methods could play a complementary role in elucidating the tertiary structure. Recently, we developed a new computational modeling method, IDP-LZerD, that can model complex structures with IDPs that are substantially longer than the usual lengths of peptides. Here, we discuss the ideas behind the IDP-LZerD pipeline with several examples.