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Bioinformatics Approaches for Predicting Disordered Protein Motifs

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Intrinsically Disordered Proteins Studied by NMR Spectroscopy

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 870))

Abstract

Short, linear motifs (SLiMs) in proteins are functional microdomains consisting of contiguous residue segments along the protein sequence, typically not more than 10 consecutive amino acids in length with less than 5 defined positions. Many positions are ‘degenerate’ thus offering flexibility in terms of the amino acid types allowed at those positions. Their short length and degenerate nature confers evolutionary plasticity meaning that SLiMs often evolve convergently. Further, SLiMs have a propensity to occur within intrinsically unstructured protein segments and this confers versatile functionality to unstructured regions of the proteome. SLiMs mediate multiple types of protein interactions based on domain-peptide recognition and guide functions including posttranslational modifications, subcellular localization of proteins, and ligand binding. SLiMs thus behave as modular interaction units that confer versatility to protein function and SLiM-mediated interactions are increasingly being recognized as therapeutic targets. In this chapter we start with a brief description about the properties of SLiMs and their interactions and then move on to discuss algorithms and tools including several web-based methods that enable the discovery of novel SLiMs (de novo motif discovery) as well as the prediction of novel occurrences of known SLiMs. Both individual amino acid sequences as well as sets of protein sequences can be scanned using these methods to obtain statistically overrepresented sequence patterns. Lists of putatively functional SLiMs are then assembled based on parameters such as evolutionary sequence conservation, disorder scores, structural data, gene ontology terms and other contextual information that helps to assess the functional credibility or significance of these motifs. These bioinformatics methods should certainly guide experiments aimed at motif discovery.

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Authors and Affiliations

  1. VIB Department of Structural Biology, Vrije Universiteit Brussel (VUB), Building E, Pleinlaan 2, 1050, Brussels, Belgium

    Pallab Bhowmick, Mainak Guharoy & Peter Tompa

  2. Institute of Enzymology, Research Center of Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary

    Peter Tompa

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  1. Pallab Bhowmick
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  2. Mainak Guharoy
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  3. Peter Tompa
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Correspondence to Peter Tompa .

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Editors and Affiliations

  1. CERM and Department of Chemistry, "Ugo Schiff" University of Florence, Florence, Italy

    Isabella C. Felli

  2. CERM and Department of Chemistry, "Ugo Schiff" University of Florence, Florence, Italy

    Roberta Pierattelli

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Bhowmick, P., Guharoy, M., Tompa, P. (2015). Bioinformatics Approaches for Predicting Disordered Protein Motifs. In: Felli, I., Pierattelli, R. (eds) Intrinsically Disordered Proteins Studied by NMR Spectroscopy. Advances in Experimental Medicine and Biology, vol 870. Springer, Cham. https://doi.org/10.1007/978-3-319-20164-1_9

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