title: A tree-based conservation scoring method for short linear motifs in multiple alignments of protein sequences.
abstract: BACKGROUND
  The structure of many eukaryotic cell regulatory proteins is highly modular. They are assembled from globular domains, segments of natively disordered polypeptides and short linear motifs. The latter are involved in protein interactions and formation of regulatory complexes. The function of such proteins, which may be difficult to define, is the aggregate of the subfunctions of the modules. It is therefore desirable to efficiently predict linear motifs with some degree of accuracy, yet sequence database searches return results that are not significant.
  
  
  RESULTS
  We have developed a method for scoring the conservation of linear motif instances. It requires only primary sequence-derived information (e.g. multiple alignment and sequence tree) and takes into account the degenerate nature of linear motif patterns. On our benchmarking, the method accurately scores 86% of the known positive instances, while distinguishing them from random matches in 78% of the cases. The conservation score is implemented as a real time application designed to be integrated into other tools. It is currently accessible via a Web Service or through a graphical interface.
  
  
  CONCLUSIONS
  The conservation score improves the prediction of linear motifs, by discarding those matches that are unlikely to be functional because they have not been conserved during the evolution of the protein sequences. It is especially useful for instances in non-structured regions of the proteins, where a domain masking filtering strategy is not applicable.
authors.affiliation: EMBL Structural and Computational Biology Unit, Meyerhofstrasse 1, 69117 Heidelberg, Germany. claudia.chica@embl.de
authors.forename: Claudia
authors.initials: C
authors.lastname: Chica
authors.forename: Alberto
authors.initials: A
authors.lastname: Labarga
authors.forename: Cathryn M
authors.initials: CM
authors.lastname: Gould
authors.forename: Rodrigo
authors.initials: R
authors.lastname: López
authors.forename: Toby J
authors.initials: TJ
authors.lastname: Gibson
mesh_terms: D000465:Algorithms; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D017124:Conserved Sequence; D016014:Linear Models; D008956:Models, Chemical; D008969:Molecular Sequence Data; D011506:Proteins / Q000737:chemistry*; D016415:Sequence Alignment / Q000379:methods*; D020539:Sequence Analysis, Protein / Q000379:methods*
chemical_list: D011506:Proteins