title: Clustering-based model of cysteine co-evolution improves disulfide bond connectivity prediction and reduces homologous sequence requirements.
abstract: BACKGROUND
  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% while requiring an order of magnitude less of aligned homologous sequences (∼10(3) instead of ∼10(4)).
  
  
  METHODS
  The software described in this article and the datasets used are available at http://ibsquare.be/sephiroth.
  
  
  BACKGROUND
  wvranken@vub.ac.be
  
  
  BACKGROUND
  Supplementary material is available at Bioinformatics online.
authors.affiliation: Interuniversity Institute of Bioinformatics in Brussels, ULB-VUB, La Plaine Campus, Triomflaan, CP 263, Structural Biology Brussels, Vrije Universiteit Brussel, Pleinlaan 2 and Structural Biology Research Center, VIB, 1050 Brussels, Belgium Interuniversity Institute of Bioinformatics in Brussels, ULB-VUB, La Plaine Campus, Triomflaan, CP 263, Structural Biology Brussels, Vrije Universiteit Brussel, Pleinlaan 2 and Structural Biology Research Center, VIB, 1050 Brussels, Belgium Interuniversity Institute of Bioinformatics in Brussels, ULB-VUB, La Plaine Campus, Triomflaan, CP 263, Structural Biology Brussels, Vrije Universiteit Brussel, Pleinlaan 2 and Structural Biology Research Center, VIB, 1050 Brussels, Belgium.
authors.forename: Daniele
authors.initials: D
authors.lastname: Raimondi
authors.affiliation: Interuniversity Institute of Bioinformatics in Brussels, ULB-VUB, La Plaine Campus, Triomflaan, CP 263, Structural Biology Brussels, Vrije Universiteit Brussel, Pleinlaan 2 and Structural Biology Research Center, VIB, 1050 Brussels, Belgium Interuniversity Institute of Bioinformatics in Brussels, ULB-VUB, La Plaine Campus, Triomflaan, CP 263, Structural Biology Brussels, Vrije Universiteit Brussel, Pleinlaan 2 and Structural Biology Research Center, VIB, 1050 Brussels, Belgium Interuniversity Institute of Bioinformatics in Brussels, ULB-VUB, La Plaine Campus, Triomflaan, CP 263, Structural Biology Brussels, Vrije Universiteit Brussel, Pleinlaan 2 and Structural Biology Research Center, VIB, 1050 Brussels, Belgium.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Orlando
authors.affiliation: Interuniversity Institute of Bioinformatics in Brussels, ULB-VUB, La Plaine Campus, Triomflaan, CP 263, Structural Biology Brussels, Vrije Universiteit Brussel, Pleinlaan 2 and Structural Biology Research Center, VIB, 1050 Brussels, Belgium Interuniversity Institute of Bioinformatics in Brussels, ULB-VUB, La Plaine Campus, Triomflaan, CP 263, Structural Biology Brussels, Vrije Universiteit Brussel, Pleinlaan 2 and Structural Biology Research Center, VIB, 1050 Brussels, Belgium Interuniversity Institute of Bioinformatics in Brussels, ULB-VUB, La Plaine Campus, Triomflaan, CP 263, Structural Biology Brussels, Vrije Universiteit Brussel, Pleinlaan 2 and Structural Biology Research Center, VIB, 1050 Brussels, Belgium.
authors.forename: Wim F
authors.initials: WF
authors.lastname: Vranken
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D016000:Cluster Analysis; D003545:Cysteine / Q000737:chemistry* / Q000145:classification / Q000235:genetics; D004220:Disulfides / Q000737:chemistry*; D006801:Humans; D015233:Models, Statistical; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D011506:Proteins / Q000032:analysis / Q000737:chemistry* / Q000235:genetics; D017385:Sequence Homology; D012984:Software
chemical_list: D004220:Disulfides; D011506:Proteins; D003545:Cysteine