AUTHOR=Craveur Pierrick , Joseph Agnel Praveen , Esque Jeremy , Narwani Tarun JaiRaj , Noel Floriane , Shinada Nicolas , Goguet Matthieu , Sylvain Léonard , Poulain Pierre , Bertrand Olivier , Faure Guilhem , Rebehmed Joseph , Ghozlane Amine , Swapna Lakshmipuram S., Bhaskara Ramachandra M., Barnoud Jonathan , Téletchéa Stéphane , Jallu Vincent , Cerny Jiri , Schneider Bohdan , Etchebest Catherine , Srinivasan Narayanaswamy , Gelly Jean-Christophe , de Brevern Alexandre G. TITLE=Protein flexibility in the light of structural alphabets JOURNAL=Frontiers in Molecular Biosciences VOLUME=2 YEAR=2015 URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2015.00020 DOI=10.3389/fmolb.2015.00020 ISSN=2296-889X 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.