Clustering-based model of cysteine co-evolution improves disulfide bond connectivity prediction and reduces homologous sequence requirements.

TitleClustering-based model of cysteine co-evolution improves disulfide bond connectivity prediction and reduces homologous sequence requirements.
Publication TypeJournal Article
Year of Publication2014
AuthorsRaimondi, D., G. Orlando, and W. F. Vranken
JournalBioinformatics
Date Published2014 Dec 8
ISSN1367-4811
Abstract

MOTIVATION: Cysteine residues have particular structural and functional relevance in proteins because of their ability to form covalent disulfide bonds. Bioinformatics tools that can accurately predict cysteine bonding states are already available, whereas it remains challenging to infer the disulfide connectivity pattern of unknown protein sequences. Improving accuracy in this area is highly relevant for the structural and functional annotation of proteins.RESULTS: We predict the intra-chain disulfide bond connectivity patterns starting from known cysteine bonding states with an evolutionary-based unsupervised approach called Sephiroth that relies on high quality alignments obtained with HHblits and is based on a coarse-grained cluster-based modelization of tandem cysteine mutations within a protein family. We compared our method with state of the art unsupervised predictors and achieve a performance improvement of 25-27% whilst requiring an order of magnitude less of aligned homologous sequences (~10(3) instead of ~10(4)). Availability: The software described in this paper and the datasets used are available at http://ibsquare.be/sephiroth .CONTACT: wvranken@vub.ac.be.

DOI10.1093/bioinformatics/btu794
Alternate JournalBioinformatics
PubMed ID25492406
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