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Protein intrinsically disordered regions have a non-random, modular architecture

Matthew Parker


Protein intrinsically disordered regions are commonly implicated in biomolecular phase separation. Classifying disordered sequences has been difficult since they lack a unifying sequence organizational principle. This short report describes the development of a statistically robust computational algorithm to quantify linear variance in amino acid composition within a protein sequence. With this approach we unexpectedly found that IDRs of both low and high sequence complexity (but not folded domains) are built from juxtaposed modules with distinct compositional bias. This concept likely represents a fundamental organizational principle of disordered sequences in the sense that it is generalizable, broadly operative, and enables the unbiased sub-division of a sequence into component parts. We hope this will provide a rational approach for pinpointing the functional regions of disordered sequences. The code for these analyses is freely available and easily implemented.