title: Direct-Coupling Analysis of nucleotide coevolution facilitates RNA secondary and tertiary structure prediction.
abstract: Despite the biological importance of non-coding RNA, their structural characterization remains challenging. Making use of the rapidly growing sequence databases, we analyze nucleotide coevolution across homologous sequences via Direct-Coupling Analysis to detect nucleotide-nucleotide contacts. For a representative set of riboswitches, we show that the results of Direct-Coupling Analysis in combination with a generalized Nussinov algorithm systematically improve the results of RNA secondary structure prediction beyond traditional covariance approaches based on mutual information. Even more importantly, we show that the results of Direct-Coupling Analysis are enriched in tertiary structure contacts. By integrating these predictions into molecular modeling tools, systematically improved tertiary structure predictions can be obtained, as compared to using secondary structure information alone.
authors.affiliation: Computational and Quantitative Biology, Sorbonne Universités, Université Pierre et Marie Curie, UMR 7238, 75006 Paris, France Computational and Quantitative Biology, CNRS, UMR 7238, 75006 Paris, France Laboratoire de Physique Statistique de l'Ecole Normale Supérieure, associé au CNRS et à l'Université Pierre et Marie Curie, 75005 Paris, France.
authors.forename: Eleonora
authors.initials: E
authors.lastname: De Leonardis
authors.affiliation: Steinbuch Centre for Computing, Karlsruher Institut für Technologie, 76133 Karlsruhe, Germany Fakultät für Physik, Karlsruher Institut für Technologie, 76133 Karlsruhe, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Lutz
authors.affiliation: Steinbuch Centre for Computing, Karlsruher Institut für Technologie, 76133 Karlsruhe, Germany Fakultät für Physik, Karlsruher Institut für Technologie, 76133 Karlsruhe, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Ratz
authors.affiliation: Laboratoire de Physique Statistique de l'Ecole Normale Supérieure, associé au CNRS et à l'Université Pierre et Marie Curie, 75005 Paris, France.
authors.forename: Simona
authors.initials: S
authors.lastname: Cocco
authors.affiliation: Laboratoire de Physique Théorique de l'Ecole Normale Supérieure, associé au CNRS et à l'Université Pierre et Marie Curie, 75005 Paris, France.
authors.forename: Rémi
authors.initials: R
authors.lastname: Monasson
authors.affiliation: Steinbuch Centre for Computing, Karlsruher Institut für Technologie, 76133 Karlsruhe, Germany schug@kit.edu.
authors.forename: Alexander
authors.initials: A
authors.lastname: Schug
authors.affiliation: Computational and Quantitative Biology, Sorbonne Universités, Université Pierre et Marie Curie, UMR 7238, 75006 Paris, France Computational and Quantitative Biology, CNRS, UMR 7238, 75006 Paris, France martin.weigt@upmc.fr.
authors.forename: Martin
authors.initials: M
authors.lastname: Weigt
mesh_terms: D000465:Algorithms; D019143:Evolution, Molecular; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D012313:RNA / Q000737:chemistry*; D058928:Riboswitch; D016415:Sequence Alignment; D017423:Sequence Analysis, RNA / Q000379:methods*; D012689:Sequence Homology, Nucleic Acid
chemical_list: D058928:Riboswitch; D012313:RNA