Describing sequence–ensemble relationships for intrinsically disordered proteins

Abstract

Intrinsically disordered proteins participate in important protein–protein and protein–nucleic acid interactions and control cellular phenotypes through their prominence as dynamic organizers of transcriptional, post-transcriptional and signalling networks. These proteins challenge the tenets of the structure–function paradigm and their functional mechanisms remain a mystery given that they fail to fold autonomously into specific structures. Solving this mystery requires a first principles understanding of the quantitative relationships between information encoded in the sequences of disordered proteins and the ensemble of conformations they sample. Advances in quantifying sequence–ensemble relationships have been facilitated through a four-way synergy between bioinformatics, biophysical experiments, computer simulations and polymer physics theories. In the present review we evaluate these advances and the resultant insights that allow us to develop a concise quantitative framework for describing the sequence–ensemble relationships of intrinsically disordered proteins.