title: DisCons: a novel tool to quantify and classify evolutionary conservation of intrinsic protein disorder.
abstract: BACKGROUND
  Analyzing the amino acid sequence of an intrinsically disordered protein (IDP) in an evolutionary context can yield novel insights on the functional role of disordered regions and sequence element(s). However, in the case of many IDPs, the lack of evolutionary conservation of the primary sequence can hamper the study of functionality, because the conservation of their disorder profile and ensuing function(s) may not appear in a traditional analysis of the evolutionary history of the protein.
  
  
  RESULTS
  Here we present DisCons (Disorder Conservation), a novel pipelined tool that combines the quantification of sequence- and disorder conservation to classify disordered residue positions. According to this scheme, the most interesting categories (for functional purposes) are constrained disordered residues and flexible disordered residues. The former residues show conservation of both the sequence and the property of disorder and are associated mainly with specific binding functionalities (e.g., short, linear motifs, SLiMs), whereas the latter class correspond to segments where disorder as a feature is important for function as opposed to the identity of the underlying sequence (e.g., entropic chains and linkers). DisCons therefore helps with elucidating the function(s) arising from the disordered state by analyzing individual proteins as well as large-scale proteomics datasets.
  
  
  CONCLUSIONS
  DisCons is an openly accessible sequence analysis tool that identifies and highlights structurally disordered segments of proteins where the conformational flexibility is conserved across homologs, and therefore potentially functional. The tool is freely available both as a web application and as stand-alone source code hosted at http://pedb.vib.be/discons .
authors.affiliation: VIB Structural Biology Research Center (SBRC), Brussels, Belgium. mvaradi@vub.ac.be.|Vrije Universiteit Brussel, Brussels, Belgium. mvaradi@vub.ac.be.
authors.forename: Mihaly
authors.initials: M
authors.lastname: Varadi
authors.affiliation: VIB Structural Biology Research Center (SBRC), Brussels, Belgium. mainak.guharoy@vib-vub.be.|Vrije Universiteit Brussel, Brussels, Belgium. mainak.guharoy@vib-vub.be.
authors.forename: Mainak
authors.initials: M
authors.lastname: Guharoy
authors.affiliation: Vrije Universiteit Brussel, Brussels, Belgium. fzsolyom@vub.ac.be.
authors.forename: Fruzsina
authors.initials: F
authors.lastname: Zsolyomi
authors.affiliation: VIB Structural Biology Research Center (SBRC), Brussels, Belgium. ptompa@vub.ac.be.|Vrije Universiteit Brussel, Brussels, Belgium. ptompa@vub.ac.be.|Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary. ptompa@vub.ac.be.
authors.forename: Peter
authors.initials: P
authors.lastname: Tompa
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D017124:Conserved Sequence; D019143:Evolution, Molecular; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D020539:Sequence Analysis, Protein / Q000379:methods*; D012984:Software; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry*
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53