title: Capturing coevolutionary signals inrepeat proteins.
abstract: BACKGROUND
  The analysis of correlations of amino acid occurrences in globular domains has led to the development of statistical tools that can identify native contacts - portions of the chains that come to close distance in folded structural ensembles. Here we introduce a direct coupling analysis for repeat proteins - natural systems for which the identification of folding domains remains challenging.
  
  
  RESULTS
  We show that the inherent translational symmetry of repeat protein sequences introduces a strong bias in the pair correlations at precisely the length scale of the repeat-unit. Equalizing for this bias in an objective way reveals true co-evolutionary signals from which local native contacts can be identified. Importantly, parameter values obtained for all other interactions are not significantly affected by the equalization. We quantify the robustness of the procedure and assign confidence levels to the interactions, identifying the minimum number of sequences needed to extract evolutionary information in several repeat protein families.
  
  
  CONCLUSIONS
  The overall procedure can be used to reconstruct the interactions at distances larger than repeat-pairs, identifying the characteristics of the strongest couplings in each family, and can be applied to any system that appears translationally symmetric.
authors.affiliation: Protein Physiology Lab, Dep de Química Biológica, Facultad de Ciencias Exactas y Naturales, UBA-CONICET-IQUIBICEN, Buenos Aires, Argentina.|Departamento de Física, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Rocío
authors.initials: R
authors.lastname: Espada
authors.affiliation: Protein Physiology Lab, Dep de Química Biológica, Facultad de Ciencias Exactas y Naturales, UBA-CONICET-IQUIBICEN, Buenos Aires, Argentina.
authors.forename: R Gonzalo
authors.initials: RG
authors.lastname: Parra
authors.affiliation: Laboratoire de physique statistique, CNRS, UPMC and École normale supérieure, 24 rue Lhomond, Paris, 75005, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Mora
authors.affiliation: , 24 rue Lhomond, Paris, 75005, France.
authors.forename: Aleksandra M
authors.initials: AM
authors.lastname: Walczak
authors.affiliation: Protein Physiology Lab, Dep de Química Biológica, Facultad de Ciencias Exactas y Naturales, UBA-CONICET-IQUIBICEN, Buenos Aires, Argentina.
authors.forename: Diego U
authors.initials: DU
authors.lastname: Ferreiro
mesh_terms: D020816:Amino Acid Motifs; D000596:Amino Acids / Q000737:chemistry*; D019143:Evolution, Molecular; D006801:Humans; D008958:Models, Molecular; D017510:Protein Folding; D055503:Protein Multimerization; D011506:Proteins / Q000737:chemistry*
chemical_list: D000596:Amino Acids; D011506:Proteins