Dark Proteome Database: Studies on Disorder

Abstract

<jats:p>There is a misconception that intrinsic disorder in proteins is equivalent to darkness. The present study aims to establish, in the scope of the Swiss-Prot and Dark Proteome databases, the relationship between disorder and darkness. Three distinct predictors were used to calculate the disorder of Swiss-Prot proteins. The analysis of the results obtained with the used predictors and visualization paradigms resulted in the same conclusion that was reached before: disorder is mostly unrelated to darkness.</jats:p>

“Protein” no longer means what it used to

“…The reasons for “darkness” may be inferred from the foregoing sections but are largely still not fully understood. We can easily predict what dark proteins are not (briefly, they are not mainly disordered ( Perdigão et al., 2020 ) nor transmembrane, whereas they have slight compositional biases ( Perdigão et al., 2015 )). Although dark proteins fit the general requirements of proteins in the proteome, our computational tools (trained with “classical” proteins) overwhelmingly fail to characterize what they actually are.…”

“…They could certainly be represented by several of the atypical arrangements we described before (scarcely included in protein Zeitgeist ), but also by folds we have not seen yet, or simply, by the lack of a structure or a given structure-function relationship. As their frequency in eukaryotic and viral proteomes is estimated to be between 26 and 55%, many of the proteins in any proteome-level study are likely to be unknown unknowns ( Perdigão et al., 2020 ).…”