A composition‐matching algorithm, <scp>MatchIDR</scp> , identifies prion‐like domains that localize to stress granules

Abstract Intrinsically disordered regions (IDRs) play important molecular roles in cells even though they do not adopt a stable structure. Relative to structured regions, IDRs have skewed amino acid compositions favoring polar and charged amino acids. This feature is a major contributor to the biophysical behavior and in vivo activity of IDRs, but the relationship between composition and activity depends strongly on which amino acids are enriched within the IDRs. Here, we present a new search algorithm, MatchIDR, that takes as input one or more IDR sequences and finds the nearest compositional matches within a proteome. Using MatchIDR with both artificially designed and native yeast IDRs as query sequences, we successfully identify IDRs from multiple organisms that localize (or do not localize) to yeast stress granules, as expected from the known activities of the query sequences. Our results demonstrate that composition‐based proteome searches can be an effective strategy for identifying new IDRs with similar in vivo activities. MatchIDR is available at https://github.com/RossLabCSU/MatchIDR .