title: Protein flexibility in the light of structural alphabets.
abstract: Protein structures are valuable tools to understand protein function. Nonetheless, proteins are often considered as rigid macromolecules while their structures exhibit specific flexibility, which is essential to complete their functions. Analyses of protein structures and dynamics are often performed with a simplified three-state description, i.e., the classical secondary structures. More precise and complete description of protein backbone conformation can be obtained using libraries of small protein fragments that are able to approximate every part of protein structures. These libraries, called structural alphabets (SAs), have been widely used in structure analysis field, from definition of ligand binding sites to superimposition of protein structures. SAs are also well suited to analyze the dynamics of protein structures. Here, we review innovative approaches that investigate protein flexibility based on SAs description. Coupled to various sources of experimental data (e.g., B-factor) and computational methodology (e.g., Molecular Dynamic simulation), SAs turn out to be powerful tools to analyze protein dynamics, e.g., to examine allosteric mechanisms in large set of structures in complexes, to identify order/disorder transition. SAs were also shown to be quite efficient to predict protein flexibility from amino-acid sequence. Finally, in this review, we exemplify the interest of SAs for studying flexibility with different cases of proteins implicated in pathologies and diseases.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U 1134 Paris, France ; UMR_S 1134, DSIMB, Université Paris Diderot, Sorbonne Paris Cite Paris, France ; Institut National de la Transfusion Sanguine, DSIMB Paris, France ; UMR_S 1134, DSIMB, Laboratory of Excellence GR-Ex Paris, France.
authors.forename: Pierrick
authors.initials: P
authors.lastname: Craveur
authors.affiliation: Rutherford Appleton Laboratory, Science and Technology Facilities Council Didcot, UK.
authors.forename: Agnel P
authors.initials: AP
authors.lastname: Joseph
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U964,7 UMR Centre National de la Recherche Scientifique 7104, IGBMC, Université de Strasbourg Illkirch, France.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Esque
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U 1134 Paris, France ; UMR_S 1134, DSIMB, Université Paris Diderot, Sorbonne Paris Cite Paris, France ; Institut National de la Transfusion Sanguine, DSIMB Paris, France ; UMR_S 1134, DSIMB, Laboratory of Excellence GR-Ex Paris, France.
authors.forename: Tarun J
authors.initials: TJ
authors.lastname: Narwani
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U 1134 Paris, France ; UMR_S 1134, DSIMB, Université Paris Diderot, Sorbonne Paris Cite Paris, France ; Institut National de la Transfusion Sanguine, DSIMB Paris, France ; UMR_S 1134, DSIMB, Laboratory of Excellence GR-Ex Paris, France.
authors.forename: Floriane
authors.initials: F
authors.lastname: Noël
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U 1134 Paris, France ; UMR_S 1134, DSIMB, Université Paris Diderot, Sorbonne Paris Cite Paris, France ; Institut National de la Transfusion Sanguine, DSIMB Paris, France ; UMR_S 1134, DSIMB, Laboratory of Excellence GR-Ex Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Shinada
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U 1134 Paris, France ; UMR_S 1134, DSIMB, Université Paris Diderot, Sorbonne Paris Cite Paris, France ; Institut National de la Transfusion Sanguine, DSIMB Paris, France ; UMR_S 1134, DSIMB, Laboratory of Excellence GR-Ex Paris, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Goguet
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U 1134 Paris, France ; UMR_S 1134, DSIMB, Université Paris Diderot, Sorbonne Paris Cite Paris, France ; Institut National de la Transfusion Sanguine, DSIMB Paris, France ; UMR_S 1134, DSIMB, Laboratory of Excellence GR-Ex Paris, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Leonard
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U 1134 Paris, France ; UMR_S 1134, DSIMB, Université Paris Diderot, Sorbonne Paris Cite Paris, France ; Institut National de la Transfusion Sanguine, DSIMB Paris, France ; UMR_S 1134, DSIMB, Laboratory of Excellence GR-Ex Paris, France ; Ets Poulain Pointe-Noire, Congo.
authors.forename: Pierre
authors.initials: P
authors.lastname: Poulain
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U 1134 Paris, France ; Institut National de la Transfusion Sanguine, DSIMB Paris, France ; UMR_S 1134, DSIMB, Laboratory of Excellence GR-Ex Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Bertrand
authors.affiliation: National Library of Medicine, National Center for Biotechnology Information, National Institutes of Health Bethesda, MD, USA.
authors.forename: Guilhem
authors.initials: G
authors.lastname: Faure
authors.affiliation: Centre National de la Recherche Scientifique UMR7590, Sorbonne Universités, Université Pierre et Marie Curie - MNHN - IRD - IUC Paris, France.
authors.forename: Joseph
authors.initials: J
authors.lastname: Rebehmed
authors.affiliation: Metagenopolis, INRA Jouy-en-Josas, France.
authors.forename: Amine
authors.initials: A
authors.lastname: Ghozlane
authors.affiliation: Molecular Biophysics Unit, Indian Institute of Science, Bangalore Bangalore, India ; Hospital for Sick Children, and Departments of Biochemistry and Molecular Genetics, University of Toronto Toronto, ON, Canada.
authors.forename: Lakshmipuram S
authors.initials: LS
authors.lastname: Swapna
authors.affiliation: Molecular Biophysics Unit, Indian Institute of Science, Bangalore Bangalore, India ; Department of Theoretical Biophysics, Max Planck Institute of Biophysics Frankfurt, Germany.
authors.forename: Ramachandra M
authors.initials: RM
authors.lastname: Bhaskara
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U 1134 Paris, France ; UMR_S 1134, DSIMB, Université Paris Diderot, Sorbonne Paris Cite Paris, France ; Institut National de la Transfusion Sanguine, DSIMB Paris, France ; UMR_S 1134, DSIMB, Laboratory of Excellence GR-Ex Paris, France ; Laboratoire de Physique, École Normale Supérieure de Lyon, Université de Lyon, Centre National de la Recherche Scientifique UMR 5672 Lyon, France.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Barnoud
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U 1134 Paris, France ; UMR_S 1134, DSIMB, Université Paris Diderot, Sorbonne Paris Cite Paris, France ; Institut National de la Transfusion Sanguine, DSIMB Paris, France ; UMR_S 1134, DSIMB, Laboratory of Excellence GR-Ex Paris, France ; Faculté des Sciences et Techniques, Université de Nantes, Unité Fonctionnalité et Ingénierie des Protéines, Centre National de la Recherche Scientifique UMR 6286, Université Nantes Nantes, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Téletchéa
authors.affiliation: Platelet Unit, Institut National de la Transfusion Sanguine Paris, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Jallu
authors.affiliation: Institute of Biotechnology, The Czech Academy of Sciences Prague, Czech Republic.
authors.forename: Jiri
authors.initials: J
authors.lastname: Cerny
authors.affiliation: Institute of Biotechnology, The Czech Academy of Sciences Prague, Czech Republic.
authors.forename: Bohdan
authors.initials: B
authors.lastname: Schneider
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U 1134 Paris, France ; UMR_S 1134, DSIMB, Université Paris Diderot, Sorbonne Paris Cite Paris, France ; Institut National de la Transfusion Sanguine, DSIMB Paris, France ; UMR_S 1134, DSIMB, Laboratory of Excellence GR-Ex Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Etchebest
authors.affiliation: Molecular Biophysics Unit, Indian Institute of Science, Bangalore Bangalore, India.
authors.forename: Narayanaswamy
authors.initials: N
authors.lastname: Srinivasan
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U 1134 Paris, France ; UMR_S 1134, DSIMB, Université Paris Diderot, Sorbonne Paris Cite Paris, France ; Institut National de la Transfusion Sanguine, DSIMB Paris, France ; UMR_S 1134, DSIMB, Laboratory of Excellence GR-Ex Paris, France.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Gelly
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U 1134 Paris, France ; UMR_S 1134, DSIMB, Université Paris Diderot, Sorbonne Paris Cite Paris, France ; Institut National de la Transfusion Sanguine, DSIMB Paris, France ; UMR_S 1134, DSIMB, Laboratory of Excellence GR-Ex Paris, France.
authors.forename: Alexandre G
authors.initials: AG
authors.lastname: de Brevern
keywords: allostery; disorder; protein complexes; protein folding; protein structures; protein—DNA interactions; secondary structure; structural alphabet