Analyzing the Sequences of Intrinsically Disordered Regions with CIDER and localCIDER

Intrinsically disordered proteins and protein regions are ubiquitous across eukaryotic proteomes where they play a range of functional roles. Unlike folded proteins, IDRs lack a well-defined native state but exist in heterogeneous ensembles of conformations. In the absence of a defined native state, structure-guided mutations to test specific mechanistic hypotheses are generally not possible. Despite this, the use of mutations to alter sequence properties has become a relatively common approach for teasing out the relationship between sequence, ensemble, and function. A key step in designing informative mutants is the ability to identify specific sequence features that may reveal an interpretable response if perturbed. Here, we provide guidance on using the CIDER and localCIDER tools for amino acid sequence analysis, with a focus on building intuition with respect to the most commonly described features.