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Disordered Function Conjunction: On the In-Silico Function Annotation of Intrinsically DisorderedRegions

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Intrinsically disorder regions (IDRs) lack a stable structure, yet perform biological functions. The functions of IDRs include mediating interactions with other molecules, including proteins, DNA, or RNA and entropic functions,… Click to show full abstract

Intrinsically disorder regions (IDRs) lack a stable structure, yet perform biological functions. The functions of IDRs include mediating interactions with other molecules, including proteins, DNA, or RNA and entropic functions, including domain linkers. Computational predictors provide residue-level indications of function for disordered proteins, which contrasts with the need to functionally annotate the thousands of experimentally and computationally discovered IDRs. In this work, we investigate the feasibility of using residue-level prediction methods for region-level function predictions. For an initial examination of the multiple function region-level prediction problem, we constructed a dataset of (likely) single function IDRs in proteins that are dissimilar to the training datasets of the residue-level function predictors. We find that available residue-level prediction methods are only modestly useful in predicting multiple region-level functions. Classification is enhanced by simultaneous use of multiple residue-level function predictions and is further improved by inclusion of amino acids content extracted from the protein sequence. We conclude that multifunction prediction for IDRs is feasible and benefits from the results produced by current residue-level function predictors, however, it has to accommodate inaccuracy in functional annotations.

Keywords: residue level; level; level function; function; level prediction

Journal Title: Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing
Year Published: 2020

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