Author: "National Institute for Health and Medical Research (INSERM), France" - Searchworks@Jio Institute Digital Library Search Results

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28 results on '"National Institute for Health and Medical Research (INSERM), France"'

1. Dynamics and deformability of α-, 310- and π-helices

Author: Tarun Jairaj Narwani, Alexandre G. de Brevern, Catherine Etchebest, Joseph Rebehmed, Nicolas K. Shinada, Pierrick Craveur, Hubert Santuz, Université Paris-Sorbonne (UP4), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA), Services and solutions for Research Informatics [Paris] (Discngine), Discngine S.A.S [Paris], Department of Integrative Structural and Computational Biology [La Jolla, CA, USA], The Scripps Research Institute [La Jolla, San Diego], Department of Computer Science and Mathematics [Lebanese American University] (CSM/SAS/LAU), Lebanese American University (LAU), This work was supported by grants from the Ministry of Research (France), University Paris Diderot, Sorbonne, Paris Cité (France), National Institute for Blood Transfusion (INTS, France), National Institute for Health and Medical Research (INSERM, France) and labex GR-Ex. The labex GR-Ex, reference ANR-11-LABX-0051 is funded by the program 'Investissements d’avenir' of the French National Research Agency, reference ANR-11-IDEX-0005-02. TN and AdB acknowledge to Indo-French Centre for the Promotion of Advanced Research / CEFIPRA for collaborative grant (number 5302-2). This work is supported by a grant from the French National Research Agency (ANR): NaturaDyRe (ANR-2010-CD2I-014-04) to JR and AdB. NSh acknowledges support from ANRT.The authors were granted access to high performance computing (HPC) resources at the French National Computing Centre CINES under grant no. c2013037147 funded by the GENCI (Grand Equipement National de Calcul Intensif). Calculations were also performed on an SGI cluster granted by Conseil Régional Ile de France and INTS (SESAME Grant)., de Brevern, Alexandre G., Scripps Research Institute, and This work was supported by grants from the Ministry of Research (France), University Paris Diderot, Sorbonne, Paris Cité (France), the National Institute for Blood Transfusion (INTS, France), the National Institute for Health and Medical Research (INSERM, France) and Labex GR-Ex. The Labex GR-Ex reference ANR-11-LABX-0051 is funded by the program 'Investissements d’avenir' of the French National Research Agency, reference ANR-11- IDEX-0005-02. TN and AdB acknowledge the Indo-French Center for the Promotion of Advanced Research/CEFIPRA for the Collaborative Grant No. 5302-2. This work was supported by a grant from the French National Research Agency (ANR): NaturaDyRe (ANR-2010-CD2I-014-04) to JR and AdB. NSh acknowledges the support from ANRT. The authors were granted access to high performance computing (HPC) resources at the French National Computing Centre CINES under Grant No. c2013037147 funded by the GENCI (Grand Equipement National de Calcul Intensif). Calculations were also performed on an SGI cluster granted by Conseil Régional Ile de France and INTS (SESAME Grant).
Subjects: 0301 basic medicine, Flexibility (anatomy), Protein domain, General Biochemistry, Genetics and Molecular Biology, flexibility, Root mean square, 03 medical and health sciences, Molecular dynamics, Protein structure, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Protein secondary structure, lcsh:QH301-705.5, Helix, Chemistry, helical local conformations, disorder, molecular dynamics, Crystallography, 030104 developmental biology, medicine.anatomical_structure, lcsh:Biology (General), structural alphabet, General Agricultural and Biological Sciences, Macromolecule, DSSP (hydrogen bond estimation algorithm)
Abstract: International audience; Protein structures are often represented as seen in crystals as (i) rigid macromolecules (ii) with helices, sheets and coils. However, both definitions are partial because (i) proteins are highly dynamic macromolecules and (ii) the description of protein structures could be more precise. With regard to these two points, we analyzed and quantified the stability of helices by considering α-helices as well as 310-and π-helices. Molecular dynamic (MD) simulations were performed on a large set of 169 representative protein domains. The local protein conformations were followed during each simulation and analyzed. The classical flexibility index (B-factor) was confronted with the MD root mean square flexibility (RMSF) index. Helical regions were classified according to their level of helicity from high to none. For the first time, a precise quantification showed the percentage of rigid and flexible helices that underlie unexpected behaviors. Only 76.4% of the residues associated with α-helices retain the conformation, while this tendency drops to 40.5% for 310-helices and is never observed for π-helices. α-helix residues that do not remain as an α-helix have a higher tendency to assume β-turn conformations than 310-or π-helices. The 310-helices that switch to the α-helix conformation have a higher B-factor and RMSF values than the average 310-helix but are associated with a lower accessibility. Rare π-helices assume a β-turn, bend and coil conformations, but not α-or 310-helices. The view on π-helices drastically changes with the new DSSP (Dictionary of Secondary Structure of Proteins) assignment approach, leading to behavior similar to 310-helices, thus underlining the importance of secondary structure assignment methods.
Published: 2017
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2. Structural variations within proteins can be as large as variations observed across their homologues

Author: Narayanaswamy Srinivasan, Bernard Offmann, Iyanar Vetrivel, Frédéric Cadet, Alexandre G. de Brevern, de Brevern, Alexandre G., Université de Paris - - Université de Paris2018 - ANR-18-IDEX-0001 - IDEX - VALID, Université Sorbonne Paris Cité - - USPC2011 - ANR-11-IDEX-0005 - IDEX - VALID, Unité de fonctionnalité et ingénierie de protéines (UFIP), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-Université Paris Cité (UPCité), Institut National de la Transfusion Sanguine [Paris] (INTS), Laboratoire d'Excellence : Biogenèse et pathologies du globule rouge (Labex Gr-Ex), Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Dynamique des Structures et Interactions des Macromolécules Biologiques - Pôle de La Réunion (DSIMB Réunion), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA), PEACCEL, Molecular Biophysics Unit, Indian Institute of Science, Région Réunion and the Fond Social Européen, Conseil Regional des Pays de la Loire in the framework of GRIOTE project, the Ministry of Research (France), University de Paris, University Paris Diderot, Sorbonne, Paris Cité (France), National Institute for Blood Transfusion (INTS, France), National Institute for Health and Medical Research (INSERM, France), Université de La Réunion, Faculty of Sciences and Technology, Indo-French Centre for the Promotion of Advanced Research / CEFIPRA for collaborative grant (number 5302-2), Department of Biotechnology, Government of India, J.C. Bose National Fellow, ANR-18-IDEX-0001,Université de Paris,Université de Paris(2018), ANR-11-IDEX-0005,USPC,Université Sorbonne Paris Cité(2011), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-Université de Paris (UP), and Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)
Subjects: 0301 basic medicine, Structural alphabet, [SDV]Life Sciences [q-bio], Datasets as Topic, Molecular Dynamics Simulation, Molecular dynamics, Biochemistry, Mice, 03 medical and health sciences, Protein structural variation, Protein structure, Protein Domains, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Databases, Protein, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Bacteria, 030102 biochemistry & molecular biology, Chemistry, Proteins, General Medicine, Protein superfamily, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Nmr data, [SDV] Life Sciences [q-bio], 030104 developmental biology, Protein conformation, Structural Homology, Protein, Structural plasticity, Biophysics
Abstract: International audience; Understanding the structural plasticity of proteins is key to understanding the intricacies of their functions and mechanistic basis. In the current study, we analyzed the available multiple crystal structures of the same protein for the structural differences. For this purpose we used an abstraction of protein structures referred as Protein Blocks (PBs) that was previously established. We also characterized the nature of the structural variations for a few proteins using molecular dynamics simulations. In both the cases, the structural variations were summarized in the form of substitution matrices of PBs. We show that certain conformational states are preferably replaced by other specific conformational states. Interestingly, these structural variations are highly similar to those previously observed across structures of homologous proteins (r 2 =0.923) or across the ensemble of conformations from NMR data (r 2 =0.919). Thus our study quantitatively shows that overall trends of structural changes in a given protein are nearly identical to the trends of structural differences that occur in the topologically equivalent positions in homologous proteins. Specific case studies are used to illustrate the nature of these structural variations.
Published: 2019
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3. Analysis of Protein Disorder Predictions in the Light of a Protein Structural Alphabet

Author: Alexandre G. de Brevern, Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA), Institut National de la Transfusion Sanguine [Paris] (INTS), Laboratoire d'Excellence : Biogenèse et pathologies du globule rouge (Labex Gr-Ex), Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Ministry of Research (France)., University of Paris, University Paris Diderot, Sorbonne Paris Cité (France)., French National Computing Centre CINES under grant no. A0070710961 by the GENCI (Grand Equipement National de Calcul Intensif)., Conseil Régional Ile de France. INTS (SESAME Grant)., University of La Réunion, Réunion Island (France)., National Institute for Health and Medical Research (INSERM, France)., National Institute for Blood Transfusion (INTS, France)., Indo-French Centre for the Promotion of Advanced Research/CEFIPRA: 5302-2., French National Computing Centre CINES under grant no. c2013037147 by the GENCI (Grand Equipement National de Calcul Intensif)., French National Computing Centre CINES under grant no. A0010707621 by the GENCI (Grand Equipement National de Calcul Intensif)., French National Computing Centre CINES under grant no. A0040710426 by the GENCI (Grand Equipement National de Calcul Intensif)., ANR-18-IDEX-0001,Université de Paris,Université de Paris(2018), ANR-11-IDEX-0005,USPC,Université Sorbonne Paris Cité(2011), ANR-19-CE17-0021,BASIN,Cibler la voie IL-3 pour inhiber la fonction basophile en conditions inflammatoires(2019), de Brevern, Alexandre G., Université de Paris - - Université de Paris2018 - ANR-18-IDEX-0001 - IDEX - VALID, Université Sorbonne Paris Cité - - USPC2011 - ANR-11-IDEX-0005 - IDEX - VALID, Cibler la voie IL-3 pour inhiber la fonction basophile en conditions inflammatoires - - BASIN2019 - ANR-19-CE17-0021 - AAPG2019 - VALID, Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)
Subjects: protein blocks, Protein Conformation, Computer science, Entropy, lcsh:QR1-502, Rigidity (psychology), Molecular Dynamics Simulation, Biochemistry, lcsh:Microbiology, 03 medical and health sciences, Molecular dynamics, intrinsic disorder regions, Protein structure, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Statistical physics, Databases, Protein, Molecular Biology, 030304 developmental biology, Flexibility (engineering), 0303 health sciences, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Continuum (topology), Communication, protein flexibility, 030302 biochemistry & molecular biology, Atom (order theory), intrinsic disorder proteins, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], mobility, molecular dynamics, Characterization (materials science), Intrinsically Disordered Proteins, nuclear magnetic resonance, Order (biology), protein structures, alpha-Synuclein, X-ray structures
Abstract: International audience; Intrinsically-disordered protein (IDP) characterization was an amazing change of paradigm in our classical sequence-structure-function theory. Moreover, IDPs are over-represented in major disease pathways and are now often targeted using small molecules for therapeutic purposes. This has had created a complex continuum from order-that encompasses rigid and flexible regions-to disorder regions; the latter being not accessible through classical crystallographic methodologies. In X-ray structures, the notion of order is dictated by access to resolved atom positions, providing rigidity and flexibility information with low and high experimental B-factors, while disorder is associated with the missing (non-resolved) residues. Nonetheless, some rigid regions can be found in disorder regions. Using ensembles of IDPs, their local conformations were analyzed in the light of a structural alphabet. An entropy index derived from this structural alphabet allowed us to propose a continuum of states from rigidity to flexibility and finally disorder. In this study, the analysis was extended to comparing these results to disorder predictions, underlying a limited correlation, and so opening new ideas to characterize and predict disorder.
Published: 2020
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4. Discrete analysis of camelid variable domains: sequences, structures, and in-silico structure prediction: Sequence-structure characteristics of VHH domains

Author: Melarkode Vattekatte, Akhila, Shinada, Nicolas Ken, Narwani, Tarun, Noël, Floriane, Bertrand, Olivier, Meyniel, Jean-Philippe, Malpertuy, Alain, Gelly, Jean-Christophe, Cadet, Frédéric, De Brevern, Alexandre, Université de La Réunion - Faculté des Sciences et Technologies (FST), Université de La Réunion (UR), Laboratoire d'Excellence : Biogenèse et pathologies du globule rouge (Labex Gr-Ex), Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Dynamique des Structures et Interactions des Macromolécules Biologiques - Pôle de La Réunion (DSIMB Réunion), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-Université de Paris (UP), Services and solutions for Research Informatics [Paris] (Discngine), Discngine S.A.S [Paris], Institut National de la Transfusion Sanguine [Paris] (INTS), Immunité et cancer (U932), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), ISoft, Atragene (Atragene), Atragene, GR-Ex, Laboratoire d'Excellence, GR-Ex, PEACCEL, Ministry of Research (France)., University Paris Diderot, Sorbonne, Paris Cité (France)., Discngine, Paris, France., ANRT, France., Conseil Régional de la Réunion., The European Social Fund EU (ESF)., French National Computing Centre CINES under grant no. A0010707621 by the GENCI (Grand Equipement National de Calcul Intensif)., French National Computing Centre CINES under grant no. A0040710426 by the GENCI (Grand Equipement National de Calcul Intensif)., University of La Réunion, Réunion Island (France)., National Institute for Blood Transfusion (INTS, France)., National Institute for Health and Medical Research (INSERM, France)., Indo-French Centre for the Promotion of Advanced Research/CEFIPRA: 5302-2., ANR-18-IDEX-0001,Université de Paris,Université de Paris(2018), and ANR-11-IDEX-0005,USPC,Université Sorbonne Paris Cité(2011)
Subjects: Frameworks, Structural alphabet, [SDV]Life Sciences [q-bio], complementarity determining regions, Bioinformatics Keywords Secondary structure, Sequence structure relationship, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, secondary structure, Subjects Biochemistry, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], nanobodies, Antibodies
Abstract: International audience; Antigen binding by antibodies requires precise orientation of the complementarity- determining region (CDR) loops in the variable domain to establish the correct contact surface. Members of the family Camelidae have a modified form of immunoglobulin gamma (IgG) with only heavy chains, called Heavy Chain only Antibodies (HCAb). Antigen binding in HCAbs is mediated by only 3 CDR loops from the single variable domain (VHH) at the N-terminus of each heavy chain. This feature of the VHH, along with other important features, e.g. easy expression, small size, thermo-stability and hydrophilicity, made them promising candidates for therapeutics and diagnostics. Thus, to design better VHH domains, it is important to thoroughly understand their sequence and structure characteristics and relationships. In this study sequence, characteristics of VHH have been analysed in depth, along with their structural features using innovative approaches, namely a structural alphabet. An elaborate summary of various studies proposing structural models of VHHs showed diversity in the algorithms used. Finally, a case study to elucidate the differences in structural models from single and multiple templates is presented. In this case study, along with the above-mentioned aspects of VHH, an exciting view of various factors in structure prediction of VHH, like template framework selection, is also discussed.
Published: 2020
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5. A structural entropy index to analyse local conformations in intrinsically disordered proteins: IDP PBs

Author: Melarkode Vattekatte, Akhila, Narwani, Tarun Jairaj, Floch, Aline, Maljković, Mirjana, Bisoo, Soubika, Shinada, Nicolas, Kranjc, Agata, Gelly, Jean-Christophe, Srinivasan, Narayanaswamy, Mitić, Nenad, de Brevern, Alexandre, de Brevern, Alexandre G., Université de Paris - - Université de Paris2018 - ANR-18-IDEX-0001 - IDEX - VALID, Université Sorbonne Paris Cité - - USPC2011 - ANR-11-IDEX-0005 - IDEX - VALID, Institut National de la Transfusion Sanguine [Paris] (INTS), Université de La Réunion - Faculté des Sciences et Technologies (FST), Université de La Réunion (UR), Laboratoire d'Excellence : Biogenèse et pathologies du globule rouge (Labex Gr-Ex), Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Dynamique des Structures et Interactions des Macromolécules Biologiques - Pôle de La Réunion (DSIMB Réunion), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-Université Paris Cité (UPCité)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-Université Paris Cité (UPCité), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-Université Paris Cité (UPCité), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), University of Belgrade, Faculty of Mathematics, Molecular Biophysics Unit, Indian Institute of Science, Discngine S.A.S [Paris], Ministry of Research (France)., University Paris Diderot, Sorbonne, Paris Cité (France)., Discngine, Paris, France., ANRT, France., Conseil Régional de la Réunion., The European Social Fund EU (ESF)., French National Computing Centre CINES under grant no. c2013037147 by the GENCI (Grand Equipement National de Calcul Intensif)., French National Computing Centre CINES under grant no. A0010707621 by the GENCI (Grand Equipement National de Calcul Intensif)., French National Computing Centre CINES under grant no. A0040710426 by the GENCI (Grand Equipement National de Calcul Intensif)., Conseil Régional Ile de France. INTS (SESAME Grant)., University of La Réunion, Réunion Island (France)., National Institute for Blood Transfusion (INTS, France)., National Institute for Health and Medical Research (INSERM, France)., Indo-French Centre for the Promotion of Advanced Research/CEFIPRA: 5302-2., ANR-18-IDEX-0001,Université de Paris,Université de Paris(2018), and ANR-11-IDEX-0005,USPC,Université Sorbonne Paris Cité(2011)
Subjects: flexibility, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], rigidity, protein structures, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, structural alphabet, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, entropy, Condensed Matter::Disordered Systems and Neural Networks, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM]
Abstract: International audience; Sequence – structure – function paradigm has been revolutionized by the discovery of disordered regions and disordered proteins more than two decades ago. While the definition of rigidity is simple with X-ray structures, the notion of flexibility is linked to high experimental B-factors. The definition of disordered regions is more complex as in these same X-ray structures; it is associated to the position of missing residues. Thus a continuum so seems to exist between rigidity, flexibility and disorder. However, it had not been precisely described. In this study, we used an ensemble of disordered proteins (or regions) and, we applied a structural alphabet to analyse their local conformation. This structural alphabet, namely Protein Blocks, had been efficiently used to highlight rigid local domains within flexible regions and so discriminates deformability and mobility concepts. Using an entropy index derived from this structural alphabet, we underlined its interest to measure these local dynamics, and to quantify, for the first time, continuum states from rigidity to flexibility and finally disorder. We also highlight non-disordered regions in the ensemble of disordered proteins in our study.
Published: 2020
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6. VHH Structural Modelling Approaches: A Critical Review

Author: Poonam Vishwakarma, Akhila Melarkode Vattekatte, Nicolas Shinada, Julien Diharce, Carla Martins, Frédéric Cadet, Fabrice Gardebien, Catherine Etchebest, Aravindan Arun Nadaradjane, Alexandre G. de Brevern, Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-Université Paris Cité (UPCité), SBX corp, PEACCEL, This work was supported by the POE FEDER 2014-20 of the Conseil Régional de La Réunion (S3D VHH program, no. SYNERGIE RE0022962), EU-H2020 and Université de la Réunion. Grants from the Ministry of Research (France), Université Paris Cité (formerly University Paris Diderot, Sorbonne, Paris Cité, France and formerly Université de Paris), Université de la Réunion, National Institute for Blood Transfusion (INTS, France), National Institute for Health and Medical Research (INSERM, France). A.G.d.B. acknowledges the Indo-French Centre for the Promotion of Advanced Research/CEFIPRA for a collaborative grant (number 5302-2)., ANR-18-IDEX-0001,Université de Paris,Université de Paris(2018), ANR-11-LABX-0051,GR-Ex,Biogenèse et pathologies du globule rouge(2011), ANR-11-IDEX-0005,USPC,Université Sorbonne Paris Cité(2011), ANR-19-CE17-0021,BASIN,Cibler la voie IL-3 pour inhiber la fonction basophile en conditions inflammatoires(2019), and European Project: FEDER
Subjects: homology and comparative modelling, [SDV]Life Sciences [q-bio], Organic Chemistry, sequence–structure relationship, deep learning, secondary structure, General Medicine, Complementarity Determining Regions, Catalysis, Computer Science Applications, Inorganic Chemistry, frameworks, docking, antibodies, threading, Physical and Theoretical Chemistry, Molecular Biology, Spectroscopy, single-domain antibody
Abstract: International audience; VHH, i.e., VH domains of camelid single-chain antibodies, are very promising therapeutic agents due to their significant physicochemical advantages compared to classical mammalian antibodies. The number of experimentally solved VHH structures has significantly improved recently, which is of great help, because it offers the ability to directly work on 3D structures to humanise or improve them. Unfortunately, most VHHs do not have 3D structures. Thus, it is essential to find alternative ways to get structural information. The methods of structure prediction from the primary amino acid sequence appear essential to bypass this limitation. This review presents the most extensive overview of structure prediction methods applied for the 3D modelling of a given VHH sequence (a total of 21). Besides the historical overview, it aims at showing how model software programs have been shaping the structural predictions of VHHs. A brief explanation of each methodology is supplied, and pertinent examples of their usage are provided. Finally, we present a structure prediction case study of a recently solved VHH structure. According to some recent studies and the present analysis, AlphaFold 2 and NanoNet appear to be the best tools to predict a structural model of VHH from its sequence.
Published: 2022
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7. Discrete analyses of protein dynamics

Author: Vattekatte, Akhila Melarkode, Narwani, Tarun, Craveur, Pierrick, Shinada, Nicolas, Floch, Aline, Santuz, Hubert, Melarkode Vattekatte, Akhila, Srinivasan, Narayanaswamy, Rebehmed, Joseph, Gelly, Jean-Christophe, Etchebest, Catherine, De Brevern, Alexandre, Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA), Institut National de la Transfusion Sanguine [Paris] (INTS), Laboratoire d'Excellence : Biogenèse et pathologies du globule rouge (Labex Gr-Ex), Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Scripps Research Institute, Discngine S.A.S [Paris], Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Molecular Biophysics Unit, Indian Institute of Science, Department of Computer Science and Mathematics [Lebanese American University] (CSM/SAS/LAU), Lebanese American University (LAU), the Ministry of Research (France), University de Paris, University Paris Diderot, Sorbonne Paris Cité (France), National Institute for Blood Transfusion (INTS, France), National Institute for Health and Medical Research (INSERM, France), Indo-French Centre for the Promotion of Advanced Research / CEFIPRA for collaborative grant (number 5302-2)., Allocation de Recherche Réunion granted by the Conseil Régional de la Réunion and the European Social Fund EU (ESF), ANRT, French National Computing Centre CINES under grant no. A0010707621 by the GENCI (Grand Equipement National de Calcul Intensif)., French National Computing Centre CINES under grant no. c2013037147 by the GENCI (Grand Equipement National de Calcul Intensif)., French National Computing Centre CINES under grant no. A0040710426 by the GENCI (Grand Equipement National de Calcul Intensif)., ANR-18-IDEX-0001,Université de Paris,Université de Paris(2018), ANR-11-IDEX-0005,USPC,Université Sorbonne Paris Cité(2011), ANR-10-CD2I-0014,NaturaDyRe,Réactions d'oxydation biocatalysées efficaces pour la synthèse de composés naturels ou énantiopurs(2010), Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), The Scripps Research Institute [La Jolla, San Diego], de Brevern, Alexandre G., Université de Paris - - Université de Paris2018 - ANR-18-IDEX-0001 - IDEX - VALID, Université Sorbonne Paris Cité - - USPC2011 - ANR-11-IDEX-0005 - IDEX - VALID, and Chimie Durable – Industries – Innovation - Réactions d'oxydation biocatalysées efficaces pour la synthèse de composés naturels ou énantiopurs - - NaturaDyRe2010 - ANR-10-CD2I-0014 - CD2I - VALID
Subjects: solvent accessibility, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Protein Conformation, Entropy, Protein Data Bank (RCSB PDB), Molecular Dynamics Simulation, Protein Structure, Secondary, 03 medical and health sciences, Molecular dynamics, Protein structure, Protein DataBank, Structural Biology, Simple (abstract algebra), [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Statistical physics, Molecular Biology, Protein secondary structure, 030304 developmental biology, Physics, 0303 health sciences, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Entropy (statistical thermodynamics), Protein dynamics, 030302 biochemistry & molecular biology, Proteins, secondary structure, General Medicine, disorder, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], molecular dynamics, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, flexibility, structural alphabet, Macromolecule, local protein conformations
Abstract: Protein structures are highly dynamic macromolecules. This dynamics is often analysed through experimental and/or computational methods only for an isolated or a limited number of proteins. Here, we explore large-scale protein dynamics simulation to observe dynamics of local protein conformations using different perspectives. We analysed molecular dynamics to investigate protein flexibility locally, using classical approaches such as RMSf, solvent accessibility, but also innovative approaches such as local entropy. First, we focussed on classical secondary structures and analysed specifically how β-strand, β-turns, and bends evolve during molecular simulations. We underlined interesting specific bias between β-turns and bends, which are considered as the same category, while their dynamics show differences. Second, we used a structural alphabet that is able to approximate every part of the protein structures conformations, namely protein blocks (PBs) to analyse (i) how each initial local protein conformations evolve during dynamics and (ii) if some exchange can exist among these PBs. Interestingly, the results are largely complex than simple regular/rigid and coil/flexible exchange. AbbreviationsNeqnumber of equivalentPBProtein BlocksPDBProtein DataBankRMSfroot mean square fluctuationsCommunicated by Ramaswamy H. Sarma.
Published: 2019
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8. Investigation of the impact of PTMs on the protein backbone conformation

Author: Tarun Jairaj Narwani, Pierrick Craveur, Alexandre G. de Brevern, Joseph Rebehmed, Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA), The SCRIPPS Research Institute (SCRIPPS), University of California [Los Angeles] (UCLA), University of California-University of California, Institut National de la Transfusion Sanguine [Paris] (INTS), Laboratoire d'Excellence : Biogenèse et pathologies du globule rouge (Labex Gr-Ex), Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Department of Computer Science and Mathematics [Lebanese American University] (CSM/SAS/LAU), Lebanese American University (LAU), the Ministry of Research (France), University de Paris, University Paris Diderot, Sorbonne, Paris Cité (France), National Institute for Blood Transfusion (INTS, France), National Institute for Health and Medical Research (INSERM, France), French National Computing Centre CINES under grant no. c2013037147 by the GENCI (Grand Equipement National de Calcul Intensif)., Indo-French Centre for the Promotion of Advanced Research / CEFIPRA for collaborative grant (number 5302-2)., Calculations were also performed on an SGI cluster granted by Conseil Régional Ile de France and INTS (SESAME Grant), ANR-18-IDEX-0001,Université de Paris,Université de Paris(2018), ANR-11-IDEX-0005,USPC,Université Sorbonne Paris Cité(2011), ANR-10-CD2I-0014,NaturaDyRe,Réactions d'oxydation biocatalysées efficaces pour la synthèse de composés naturels ou énantiopurs(2010), de Brevern, Alexandre G., Université de Paris - - Université de Paris2018 - ANR-18-IDEX-0001 - IDEX - VALID, Université Sorbonne Paris Cité - - USPC2011 - ANR-11-IDEX-0005 - IDEX - VALID, Chimie Durable – Industries – Innovation - Réactions d'oxydation biocatalysées efficaces pour la synthèse de composés naturels ou énantiopurs - - NaturaDyRe2010 - ANR-10-CD2I-0014 - CD2I - VALID, The Scripps Research Institute [La Jolla, San Diego], and Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)
Subjects: 0301 basic medicine, Models, Molecular, Glycosylation, Protein Conformation, Entropy, Clinical Biochemistry, N-glycosylation, Proteomics, Quantitative Biology - Quantitative Methods, Biochemistry, liver carboxylesterase, Carboxylesterase, Protein structure, N-linked glycosylation, Peptide bond, deformability, Databases, Protein, renin endopeptidase, Quantitative Methods (q-bio.QM), [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], biology, Chemistry, phosphorylation, Methylation, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], mobility, rigidity, statistics, Phosphorylation, actin, cyclin-dependent kinase 2 (CDK2), Computational biology, 03 medical and health sciences, Endopeptidases, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Actin, 030102 biochemistry & molecular biology, Organic Chemistry, Cyclin-dependent kinase 2, Cyclin-Dependent Kinase 2, Proteins, Biomolecules (q-bio.BM), Actins, 030104 developmental biology, Quantitative Biology - Biomolecules, FOS: Biological sciences, biology.protein, methylation, Protein Processing, Post-Translational
Abstract: International audience; Post-Translational Modifications (PTMs) are known to play a critical role in the regulation of the protein functions. Their impact on protein structures, and their link to disorder regions have already been spotted on the past decade. Nonetheless, the high diversity of PTMs types, and the multiple schemes of protein modifications (multiple PTMs, of different types, at different time, etc) make difficult the direct confrontation of PTM annotations and protein structures data.We so analyzed the impact of the residue modifications on the protein structures at local level. Thanks to a dedicated structure database, namely PTM-SD, a large screen of PTMs have been done and analyze at a local protein conformation levels using the structural alphabet Protein Blocks (PBs). We investigated the relation between PTMs and the backbone conformation of modified residues, of their local environment, and at the level of the complete protein structure. The two main PTM types (N-glycosylation and phosphorylation) have been studied in non-redundant datasets, and then, 4 different proteins were focused, covering 3 types of PTMs: N-glycosylation in renin endopeptidase and liver carboxylesterase, phosphorylation in cyclin-dependent kinase 2 (CDK2), and methylation in actin. We observed that PTMs could either stabilize or destabilize the backbone structure, at a local and global scale, and that these effects depend on the PTM types.
Published: 2019
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9. A minimum set of stable blocks for rational design of polypeptide chains Running head: A set of stable blocks for protein rational design

Author: Nekrasov, Alexei, Alekseeva, Ludmila, Pogosyan, Rudolf A., Dolgikh, Dmitry, Kirpichnikov, M. P., de Brevern, Alexandre, Anashkina, Anastasia, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry (IBCh RAS), Russian Academy of Sciences [Moscow] (RAS), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA), Institut National de la Transfusion Sanguine [Paris] (INTS), Laboratoire d'Excellence : Biogenèse et pathologies du globule rouge (Labex Gr-Ex), Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Engelhardt Institute of Molecular Biology (ISTC), Indo-French Centre for the Promotion of Advanced Research / CEFIPRA for collaborative grant (number 5302-2), the Ministry of Research (France), University de Paris, University Paris Diderot, Sorbonne, Paris Cité (France), National Institute for Blood Transfusion (INTS, France), National Institute for Health and Medical Research (INSERM, France), Russian Foundation for Basic Research (#18-54-00037), Program for Molecular and Cellular Biology of the Russian Academy of Sciences, Russian Science Foundation (grant #14-14-01152), ANR-18-IDEX-0001,Université de Paris,Université de Paris(2018), ANR-11-IDEX-0005,USPC,Université Sorbonne Paris Cité(2011), de Brevern, Alexandre G., Université de Paris - - Université de Paris2018 - ANR-18-IDEX-0001 - IDEX - VALID, Université Sorbonne Paris Cité - - USPC2011 - ANR-11-IDEX-0005 - IDEX - VALID, and Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)
Subjects: [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Quantitative Biology - Biomolecules, FOS: Biological sciences, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Biomolecules (q-bio.BM), [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Quantitative Biology - Quantitative Methods, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Quantitative Methods (q-bio.QM), [SDV.BIO] Life Sciences [q-bio]/Biotechnology
Abstract: International audience; The aim of this work was to find a minimal set of structurally stable pentapeptides, which allows forming a polypeptide chain of a required 3D structure. To search for factors that ensure structural stability of the pentapeptide, we generated peptide sequences with no more than three functional groups, based on the alanine pentapeptide AAAAA. We analyzed 44,860 structures of peptides by the molecular dynamics method and found that 1,225 pentapeptides over 80% of the simulation time were in a stable conformation. Clustering of these conformations revealed 54 topological types of conformationally stable pentapeptides. These conformations relate to different combined elements of the protein secondary structure. So, we obtained a minimal set of amino acid structures of conformationally stable pentapeptides, creating a complete set of different topologies that ensure the formation of pre-folded conformation of protein structures.
Published: 2019
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10. Long-range molecular dynamics show that inactive forms of Protein Kinase A are more dynamic than active forms

Author: Kalaivani, R., Narwani, T. J., de Brevern, A. G., Srinivasan, N., de Brevern, Alexandre G., Université Sorbonne Paris Cité - - USPC2011 - ANR-11-IDEX-0005 - IDEX - VALID, Université de Paris - - Université de Paris2018 - ANR-18-IDEX-0001 - IDEX - VALID, Molecular Biophysics Unit, Indian Institute of Science, Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-Université Paris Cité (UPCité), Institut National de la Transfusion Sanguine [Paris] (INTS), Laboratoire d'Excellence : Biogenèse et pathologies du globule rouge (Labex Gr-Ex), Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), the Ministry of Research (France), University de Paris, University Paris Diderot, Sorbonne Paris Cité (France), Fund for Improve- ment of Science and Technology infrastructure (FIST), DST, Centre for Advanced Structures (CAS), University Grants Commission (UGC), National Institute for Blood Transfusion (INTS, France), National Institute for Health and Medical Research (INSERM, France), Indo-French Centre for the Promotion of Advanced Research / CEFIPRA for collaborative grant (number 5302-2)., Indian Institute of Science-Department of Biotechnol- ogy partnership program, Mathematical Biology program of Department of Science and Technology, J.C. Bose National Fellow, ANR-11-IDEX-0005,USPC,Université Sorbonne Paris Cité(2011), ANR-18-IDEX-0001,Université de Paris,Université de Paris(2018), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-Université de Paris (UP), and Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)
Subjects: active and inactive states, structural flexibility in active and inactive state kinases, protein kinases, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Protein Conformation, functional state, Full‐Length Papers, [SDV]Life Sciences [q-bio], Molecular Dynamics Simulation, Cyclic AMP-Dependent Protein Kinases, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], molecular dynamics, Enzyme Activation, [SDV] Life Sciences [q-bio], Mice, Catalytic Domain, STY kinases, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, protein kinase A, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Phosphorylation
Abstract: International audience; Many protein kinases are characterized by at least two structural forms corresponding to the highest level of activity (active) and low or no activity, (inactive). Further, protein dynamics is an important consideration in understanding the molecular and mechanistic basis of enzyme function. In this work, we use protein kinase A (PKA) as the model system and perform microsecond range molecular dynamics (MD) simulations on six variants which differ from one another in terms of active and inactive form, with or without bound ligands, C-terminal tail and phosphorylation at the activation loop. We find that the root mean square fluctuations in the MD simulations are generally higher for the inactive forms than the active forms. This difference is statistically significant. The higher dynamics of inactive states has significant contributions from ATP binding loop, catalytic loop, and αG helix. Simulations with and without C-terminal tail show this differential dynamics as well, with lower dynamics both in the active and inactive forms if C-terminal tail is present. Similarly, the dynamics associated with the inactive form is higher irrespective of the phosphorylation status of Thr 197. A relatively stable stature of active kinases may be better suited for binding of substrates and detachment of the product. Also, phosphoryl group transfer from ATP to the phosphosite on the substrate requires precise transient coordination of chemical entities from three different molecules, which may be facilitated by the higher stability of the active state.
Published: 2019
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11. A structural entropy index to analyse local conformations in intrinsically disordered proteins

Author: Nicolas K. Shinada, Alexandre G. de Brevern, Nenad S. Mitić, Melarkode Vattekatte Akhila, Mirjana Maljković, Agata Kranjc, Tarun Jairaj Narwani, Narayanaswamy Srinivasan, Jean-Christophe Gelly, Soubika Bisoo, Aline Floch, Institut National de la Transfusion Sanguine [Paris] (INTS), Université de La Réunion - Faculté des Sciences et Technologies (FST), Université de La Réunion (UR), Laboratoire d'Excellence : Biogenèse et pathologies du globule rouge (Labex Gr-Ex), Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Dynamique des Structures et Interactions des Macromolécules Biologiques - Pôle de La Réunion (DSIMB Réunion), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-Université Paris Cité (UPCité)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-Université Paris Cité (UPCité), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-Université Paris Cité (UPCité), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), University of Belgrade, Faculty of Mathematics, Molecular Biophysics Unit, Indian Institute of Science, Discngine S.A.S [Paris], Ministry of Research (France)., University Paris Diderot, Sorbonne, Paris Cité (France)., Discngine, Paris, France., ANRT, France., Conseil Régional de la Réunion., The European Social Fund EU (ESF)., French National Computing Centre CINES under grant no. c2013037147 by the GENCI (Grand Equipement National de Calcul Intensif)., French National Computing Centre CINES under grant no. A0010707621 by the GENCI (Grand Equipement National de Calcul Intensif)., French National Computing Centre CINES under grant no. A0040710426 by the GENCI (Grand Equipement National de Calcul Intensif)., Conseil Régional Ile de France. INTS (SESAME Grant)., University of La Réunion, Réunion Island (France)., National Institute for Blood Transfusion (INTS, France)., National Institute for Health and Medical Research (INSERM, France)., Indo-French Centre for the Promotion of Advanced Research/CEFIPRA: 5302-2., ANR-18-IDEX-0001,Université de Paris,Université de Paris(2018), ANR-11-IDEX-0005,USPC,Université Sorbonne Paris Cité(2011), Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-Université de Paris (UP)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-Université de Paris (UP), and Institut National de la Transfusion Sanguine [Paris] (INTS)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-Université de Paris (UP)
Subjects: Physics, 0303 health sciences, Structural entropy, Local conformation, Protein Conformation, 030302 biochemistry & molecular biology, Intrinsically disordered proteins, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Condensed Matter::Disordered Systems and Neural Networks, Intrinsically Disordered Proteins, flexibility, 03 medical and health sciences, Generalized entropy index, Protein structure, rigidity, Structural Biology, protein structures, Entropy (information theory), structural alphabet, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Structural alphabet, Statistical physics, entropy, 030304 developmental biology
Abstract: International audience; Sequence – structure – function paradigm has been revolutionized by the discovery of disordered regions and disordered proteins more than two decades ago. While the definition of rigidity is simple with X-ray structures, the notion of flexibility is linked to high experimental B-factors. The definition of disordered regions is more complex as in these same X-ray structures; it is associated to the position of missing residues. Thus a continuum so seems to exist between rigidity, flexibility and disorder. However, it had not been precisely described. In this study, we used an ensemble of disordered proteins (or regions) and, we applied a structural alphabet to analyse their local conformation. This structural alphabet, namely Protein Blocks, had been efficiently used to highlight rigid local domains within flexible regions and so discriminates deformability and mobility concepts. Using an entropy index derived from this structural alphabet, we underlined its interest to measure these local dynamics, and to quantify, for the first time, continuum states from rigidity to flexibility and finally disorder. We also highlight non-disordered regions in the ensemble of disordered proteins in our study.
Published: 2020
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12. Discrete analysis of camelid variable domains: sequences, structures, and in-silico structure prediction

Author: Frédéric Cadet, Nicolas K. Shinada, Olivier Bertrand, Floriane Noël, Alexandre G. de Brevern, Alain Malpertuy, Jean-Christophe Gelly, Jean-Philippe Meyniel, Tarun Jairaj Narwani, Akhila Melarkode Vattekatte, Université de La Réunion - Faculté des Sciences et Technologies (FST), Université de La Réunion (UR), Laboratoire d'Excellence : Biogenèse et pathologies du globule rouge (Labex Gr-Ex), Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Dynamique des Structures et Interactions des Macromolécules Biologiques - Pôle de La Réunion (DSIMB Réunion), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-Université de Paris (UP), Services and solutions for Research Informatics [Paris] (Discngine), Discngine S.A.S [Paris], Institut National de la Transfusion Sanguine [Paris] (INTS), Immunité et cancer (U932), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), ISoft, Atragene (Atragene), Atragene, GR-Ex, Laboratoire d'Excellence, GR-Ex, PEACCEL, Ministry of Research (France)., University Paris Diderot, Sorbonne, Paris Cité (France)., Discngine, Paris, France., ANRT, France., Conseil Régional de la Réunion., The European Social Fund EU (ESF)., French National Computing Centre CINES under grant no. A0010707621 by the GENCI (Grand Equipement National de Calcul Intensif)., French National Computing Centre CINES under grant no. A0040710426 by the GENCI (Grand Equipement National de Calcul Intensif)., University of La Réunion, Réunion Island (France)., National Institute for Blood Transfusion (INTS, France)., National Institute for Health and Medical Research (INSERM, France)., Indo-French Centre for the Promotion of Advanced Research/CEFIPRA: 5302-2., ANR-18-IDEX-0001,Université de Paris,Université de Paris(2018), and ANR-11-IDEX-0005,USPC,Université Sorbonne Paris Cité(2011)
Subjects: Bioinformatics, Computer science, [SDV]Life Sciences [q-bio], Structural alphabet, In silico, Bioinformatics Keywords Secondary structure, Discrete analysis, lcsh:Medicine, Complementarity determining region, Computational biology, Subjects Biochemistry, Biochemistry, Antibodies, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Secondary structure, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Protein secondary structure, Complementarity determining regions, 030304 developmental biology, 0303 health sciences, Heavy chain, Frameworks, General Neuroscience, lcsh:R, 030302 biochemistry & molecular biology, General Medicine, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, Template, Complementarity (molecular biology), Sequence structure relationship, Nanobodies, General Agricultural and Biological Sciences
Abstract: Antigen binding by antibodies requires precise orientation of the complementarity- determining region (CDR) loops in the variable domain to establish the correct contact surface. Members of the family Camelidae have a modified form of immunoglobulin gamma (IgG) with only heavy chains, called Heavy Chain only Antibodies (HCAb). Antigen binding in HCAbs is mediated by only three CDR loops from the single variable domain (VHH) at the N-terminus of each heavy chain. This feature of the VHH, along with their other important features, e.g., easy expression, small size, thermo-stability and hydrophilicity, made them promising candidates for therapeutics and diagnostics. Thus, to design better VHH domains, it is important to thoroughly understand their sequence and structure characteristics and relationship. In this study, sequence characteristics of VHH domains have been analysed in depth, along with their structural features using innovative approaches, namely a structural alphabet. An elaborate summary of various studies proposing structural models of VHH domains showed diversity in the algorithms used. Finally, a case study to elucidate the differences in structural models from single and multiple templates is presented. In this case study, along with the above-mentioned aspects of VHH, an exciting view of various factors in structure prediction of VHH, like template framework selection, is also discussed.
Published: 2020
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13. In silico prediction of protein flexibility with local structure approach

Author: Sylvain Leonard, Pierrick Craveur, Jean-Christophe Gelly, Narayanaswamy Srinivasan, Joseph Rebehmed, Catherine Etchebest, Tarun Jairaj Narwani, Alexandre G. de Brevern, Aurélie Bornot, Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA), Institut National de la Transfusion Sanguine [Paris] (INTS), Laboratoire d'Excellence : Biogenèse et pathologies du globule rouge (Labex Gr-Ex), Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Scripps Research Institute, Molecular Graphics Laboratory (MGL), Lebanese American University (LAU), Molecular Biophysics Unit, Indian Institute of Science, the Ministry of Research (France), University de Paris, University Paris Diderot, Sorbonne, Paris Cité (France), National Institute for Blood Transfusion (INTS, France), National Institute for Health and Medical Research (INSERM, France), Indo-French Centre for the Promotion of Advanced Research / CEFIPRA for collaborative grant (number 5302-2), French National Computing Centre CINES under grant no. c2013037147 by the GENCI (Grand Equipement National de Calcul Intensif), French National Computing Centre CINES under grant no. c2016077621 by the GENCI (Grand Equipement National de Calcul Intensif), French National Computing Centre CINES under grant no. A0010707621 by the GENCI (Grand Equipement National de Calcul Intensif), ANR-18-IDEX-0001,Université de Paris,Université de Paris(2018), ANR-11-IDEX-0005,USPC,Université Sorbonne Paris Cité(2011), de Brevern, Alexandre G., Université de Paris - - Université de Paris2018 - ANR-18-IDEX-0001 - IDEX - VALID, Université Sorbonne Paris Cité - - USPC2011 - ANR-11-IDEX-0005 - IDEX - VALID, Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), and The Scripps Research Institute [La Jolla, San Diego]
Subjects: 0301 basic medicine, Bioinformatics, Protein Conformation, Datasets as Topic, Long Structural Prototypes, Molecular Dynamics Simulation, Biochemistry, Quantitative Biology - Quantitative Methods, 03 medical and health sciences, Matrix (mathematics), Structural bioinformatics, Protein structure, Protein Data Bank, evolutionary information, Support Vector Machines, Feature (machine learning), [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Representation (mathematics), Databases, Protein, Quantitative Methods (q-bio.QM), protein folds, Mathematics, Flexibility (engineering), [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 030102 biochemistry & molecular biology, Proteins, Biomolecules (q-bio.BM), General Medicine, computer.file_format, disorder, Structural Bioinformatics, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Support vector machine, 030104 developmental biology, Quantitative Biology - Biomolecules, FOS: Biological sciences, structural alphabet, Biological system, computer, amino acid, Software
Abstract: International audience; Flexibility is an intrinsic essential feature of protein structures, directly linked to their functions. To this day, most of the prediction methods use the crystallographic data (namely B-factors) as the only indicator of protein’s inner flexibility and predicts them as rigid or flexible.PredyFlexy stands differently from other approaches as it relies on the definition of protein flexibility (i) not only taken from crystallographic data, but also (ii) from Root Mean Square Fluctuation (RMSFs) observed in Molecular Dynamics simulations. It also uses a specific representation of protein structures, named Long Structural Prototypes (LSPs). From Position-Specific Scoring Matrix, the 120 LSPs are predicted with a good accuracy and directly used to predict (i) the protein flexibility in three categories (flexible, intermediate and rigid), (ii) the normalized B-factors, (iii) the normalized RMSFs, and (iv) a confidence index. Prediction accuracy among these three classes is equivalent to the best two class prediction methods, while the normalized B-factors and normalized RMSFs have a good correlation with experimental and in silico values. Thus, PredyFlexy is a unique approach, which is of major utility for the scientific community. It support parallelization features and can be run on a local cluster using multiple cores.The entire project is available under an open-source license at http://www.dsimb.inserm.fr/~debrevern/TOOLS/predyflexy_1.3/index.php.
Published: 2018
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14. Recent advances on polyproline II

Author: Alexandre G. de Brevern, Nicolas K. Shinada, Tarun Jairaj Narwani, Narayanasamy Srinivasan, Akhila Melarkode Vattekatte, Jean-Christophe Gelly, Yassine Ghouzam, Hubert Santuz, Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA), Discngine, SAS, Dynamique des Structures et Interactions des Macromolécules Biologiques - Pôle de La Réunion (DSIMB Réunion), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA), Molecular Biophysics Unit, Indian Institute of Sciences (MBU), Indian Institute of Science [Bangalore] (IISc Bangalore), Grants from the Ministry of Research (France), University Paris Diderot, Sorbonne, Paris Cité (France), National Institute for Blood Transfusion (INTS, France), National Institute for Health and Medical Research (INSERM, France) and labex GR-Ex. The labex GR-Ex, reference ANR-11-LABX-0051 is funded by the program 'Investissements d’avenir' of the French National Research Agency, reference ANR-11-IDEX-0005-02. TjrN, NSr and AdB acknowledge to Indo-French Centre for the Promotion of Advanced Research / CEFIPRA for collaborative grant (number 5302-2). NSh acknowledges support from ANRT., and de Brevern, Alexandre G.
Subjects: 0301 basic medicine, Models, Molecular, Globular protein, Stereochemistry, Structural alphabet, Clinical Biochemistry, Computational biology, Biochemistry, Protein Structure, Secondary, 03 medical and health sciences, Protein structure, Secondary structure, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Protein secondary structure, Region analysis, Polyproline helix, chemistry.chemical_classification, 030102 biochemistry & molecular biology, Frameworks, Chemistry, Protein dynamics, Organic Chemistry, Structure and function, 030104 developmental biology, Helix, Sequence structure relationship, Peptides, Local protein conformations
Abstract: International audience; About half of the globular proteins are composed of regular secondary structures, α-helices, and β-sheets, while the rest are constituted of irregular secondary structures, such as turns or coil conformations. Other regular secondary structures are often ignored, despite their importance in biological processes. Among such structures, the polyproline II helix (PPII) has interesting behaviours. PPIIs are not usually associated with conventional stabilizing interactions, and recent studies have observed that PPIIs are more frequent than anticipated. In addition, it is suggested that they may have an important functional role, particularly in protein-protein or protein-nucleic acid interactions and recognition. Residues associated with PPII conformations represent nearly 5% of the total residues, but the lack of PPII assignment approaches prevents their systematic analysis. This short review will present current knowledge and recent research in PPII area. In a first step, the different methodologies able to assign PPII are presented. In the second step, recent studies that have shown new perspectives in PPII analysis in terms of structure and function are underlined with three cases: (1) PPII in protein structures. For instance, the first crystal structure of an oligoproline adopting an all-trans polyproline II (PPII) helix had been presented; (2) the involvement of PPII in different diseases and drug designs; and (3) an interesting extension of PPII study in the protein dynamics. For instance, PPIIs are often linked to disorder region analysis and the precise analysis of a potential PPII helix in hypogonadism shows unanticipated PPII formations in the patient mutation, while it is not observed in the wild-type form of KISSR1 protein.
Published: 2017
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15. Bioinformatic analysis of the protein/DNA interface

Author: Daniel Svozil, Jiří Černý, Bohdan Schneider, Alexandre G. de Brevern, Agnel Praveen Joseph, Jean-Christophe Gelly, de Brevern, Alexandre G., Institute of Biotechnology AS CR, Laboratory of Informatics and Chemistry, Institute of Chemical Technology [Prague] (ICT), GR-Ex, Laboratoire d'Excellence, GR-Ex, Dynamique des Structures et Interactions des Macromolécules Biologiques (DSIMB), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), The Czech-France collaboration Barrande [MEB021032], BIOCEV CZ.1.05/1.1.00/02.0109 from the ERDF, [P305/ 80 12/1801] from the Czech Science Foundation, and institutional [AV0Z50520701], supported by [MSM 6046137302 to D.S. and P.Č.], and supported by the Ministry of Research (France), University Paris Diderot, Sorbonne Paris Cité (France), National Institute of Blood Transfusion (INTS, France), National Institute of Health and Medical Research (INSERM, France) and 'Investissements d'avenir', Laboratories of Excellence GR-Ex (France) (to J.C.G. and A.G.dB.). Funding for open access charge: Czech Science Foundation and Academy of Sciences of the Czech Republic.
Subjects: Models, Molecular, Protein Conformation, DNA interface, Crystal structure, Plasma protein binding, Pentapeptide repeat, chemistry.chemical_compound, 0302 clinical medicine, structural alphabet: Protein Blocks, MESH: Protein Conformation, Protein structure, Structural Biology, Structural motif, Conformational isomerism, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM], Genetics, 0303 health sciences, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], MESH: DNA, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], DNA-Binding Proteins, MESH: Nucleic Acid Conformation, Naked DNA, Data Interpretation, Statistical, MESH: Phosphates, MESH: Models, Molecular, Protein Binding, MESH: Computational Biology, Stereochemistry, Biophysics, Biology, DNA-binding protein, Phosphates, 03 medical and health sciences, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Water, MESH: Protein Binding, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Transcription factor, 030304 developmental biology, Computational Biology, Water, DNA structure, DNA, Base (topology), Crystallography, chemistry, protein structures, Nucleic acid, Nucleic Acid Conformation, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], DNA interactions, protein, MESH: Data Interpretation, Statistical, 030217 neurology & neurosurgery, MESH: DNA-Binding Proteins
Abstract: Despite extensive studies of the geometry of protein/DNA interfaces the understanding of the affinity and specificity of the protein/DNA interactions remains elusive. We present a novel approach to geometric analysis of protein/nucleic acid interfaces that is based on classification of their local conformations. Protein structures are divided into a series of pentapeptide fragments and each is assigned one of 16 conformers or ‘protein blocks’ [de Brevern et al. Proteins 41, 271 (2000)]. Similarly, each DNA step (unit [base]sugar-phosphate-sugar[base]) is assigned one of ∼20 DNA conformers [Svozil et al. NAR 36, 3690 (2008)]. Significantly, local structures classified into distinct conformers can be represented by symbols so that they can be analyzed more easily than complicated 3D objects. Size of the fragments used for the classification allows analysis of structural features of the interface at a scale intermediate between too detailed interatomic contacts on one side and too crude protein motifs (helix-turn-helix, Zn-finger, ...) on the other. We will present correlations between protein and DNA conformers at their interface from more than 15 hundred protein/DNA crystal structures broken by various criteria of the analyzed structures as protein functional classification, e.g. in GO or Pfam or by crystallographic properties, resolution or overall structure quality.Acknowledgments. This work was supported by Czech-France collaboration Barrande (MEB021032) and Czech Science Foundation (P305/10/2184).
Published: 2013
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16. Understanding the role of domain–domain linkers in the spatial orientation of domains in multi-domain proteins

Author: Alexandre G. de Brevern, Ramachandra M. Bhaskara, Narayanaswamy Srinivasan, de Brevern, Alexandre G., Molecular Biophysics Unit, Indian Institute of Science, GR-Ex, Laboratoire d'Excellence, GR-Ex, Dynamique des Structures et Interactions des Macromolécules Biologiques (DSIMB), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Indo-French collaborative grant (CEFIPRA/IFCPAR 3903-E) The Ministry of Research (France) The University Paris Diderot, Sorbonne Paris Cite (France) The National Institute of Blood Transfusion (INTS, France) The National Institute of Health and Medical Research (INSERM, France) The Laboratories of Excellence, GR-Ex (France) Department of Biotechnology (India)
Subjects: Models, Molecular, Protein Conformation, Interface (Java), 030303 biophysics, linker flexibility, Sequence (biology), Biochemistry, Local structure, Domain (software engineering), 03 medical and health sciences, Structural Biology, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Computer Simulation, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, interface constraints, multi-domain proteins, Molecular Biology, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM], 030304 developmental biology, Flexibility (engineering), 0303 health sciences, Binding Sites, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Orientation (computer vision), Chemistry, Proteins, General Medicine, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Protein Structure, Tertiary, Multi domain, Crystallography, inter-domain orientation, inter-domain linkers, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Biological system, Linker, Algorithms, Protein Binding
Abstract: International audience; Inter-domain linkers (IDLs)' bridge flanking domains and support inter-domain communication in multi-domain proteins. Their sequence and conformational preferences enable them to carry out varied functions. They also provide sufficient flexibility to facilitate domain motions and, in conjunction with the interacting interfaces, they also regulate the inter-domain geometry (IDG). In spite of the basic intuitive understanding of the inter-domain orientations with respect to linker conformations and interfaces, we still do not entirely understand the precise relationship among the three. We show that IDG is evolutionarily well conserved and is constrained by the domain-domain interface interactions. The IDLs modulate the interactions by varying their lengths, conformations and local structure, thereby affecting the overall IDG. Results of our analysis provide guidelines in modelling of multi-domain proteins from the tertiary structures of constituent domain components.
Published: 2013
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17. Trends in IT Innovation to Build a Next Generation Bioinformatics Solution to Manage and Analyse Biological Big Data Produced by NGS Technologies

Author: de Brevern, Alexandre G., Meyniel, Jean-Philippe, Fairhead, Cecile, Neuvéglise, Cécile, Malpertuy, Alain, Université Paris Diderot - Paris 7 (UPD7), ISoft, Institut de génétique et microbiologie [Orsay] (IGM), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Atragene, Ministry of Research (France), University Paris Diderot, Sorbonne, Paris Cite (France), National Institute for Blood Transfusion (INTS, France), National Institute for Health and Medical Research (INSERM, France), labex GR-Ex, University Paris Sud, CNRS, INRA, AgroParisTech, ISOFT, ATRAGENE, and program 'Investissements d'avenir' of the French National Research Agency [11-LABX-0051, ANR-11-IDEX-0005-02]
Subjects: Databases, Factual, [SDV]Life Sciences [q-bio], lcsh:R, lcsh:Medicine, Computational Biology, High-Throughput Nucleotide Sequencing, Humans, Review Article, Genomics, Software
Abstract: International audience; Sequencing the human genome began in 1994, and 10 years of work were necessary in order to provide a nearly complete sequence. Nowadays, NGS technologies allow sequencing of a whole human genome in a few days. This deluge of data challenges scientists in many ways, as they are faced with data management issues and analysis and visualization drawbacks due to the limitations of current bioinformatics tools. In this paper, we describe how the NGS Big Data revolution changes the way of managing and analysing data. We present how biologists are confronted with abundance of methods, tools, and data formats. To overcome these problems, focus on Big Data Information Technology innovations from web and business intelligence. We underline the interest of NoSQL databases, which are much more efficient than relational databases. Since Big Data leads to the loss of interactivity with data during analysis due to high processing time, we describe solutions from the Business Intelligence that allow one to regain interactivity whatever the volume of data is. We illustrate this point with a focus on the Amadea platform. Finally, we discuss visualization challenges posed by Big Data and present the latest innovations with JavaScript graphic libraries.
Published: 2015
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18. Pre-diagnostic concordance with the WCRF/AICR guidelines and survival in European colorectal cancer patients: a cohort study

Author: Carla H. van Gils, E. Riboli, Christos Tsironis, Anne-Claire Vergnaud, H. Bas Bueno-de-Mesquita, Laureen Dartois, José Ramón Quirós, Veronika Fedirko, Pietro Ferrari, Teresa Norat, Pagona Lagiou, Christina C. Dahm, Giovanna Masala, Timothy J. Key, Mark J. Gunter, Maria Wennberg, Kay-Tee Khaw, Verena Katzke, Petra H.M. Peeters, Aurelio Barricarte, Heather Ward, Nicholas J. Wareham, Anne Tjønneland, Lena Maria Nilsson, Bodil Ohlsson, Valeria Pala, Laure Dossus, Antonia Trichopoulou, Tilman Kühn, Heiner Boeing, Elisabete Weiderpass, Petra A. Wark, M. Dorronsoro, Carmen Navarro, Camilla Plambeck Hansen, Genevieve Buckland, Salvatore Panico, Marie-Christine Boutron-Ruault, María José Sánchez, Paolo Vineis, Peter D. Siersema, Karin Jirström, Dora Romaguera, Rosario Tumino, Mazda Jenab, Romaguera, Dora, Ward, Heather, Wark, Petra A, Vergnaud, Anne Claire, Peeters, Petra H, van Gils, Carla H, Ferrari, Pietro, Fedirko, Veronika, Jenab, Mazda, Boutron Ruault, Marie Christine, Dossus, Laure, Dartois, Laureen, Hansen, Camilla Plambeck, Dahm, Christina Catherine, Buckland, Genevieve, Sánchez, María José, Dorronsoro, Miren, Navarro, Carmen, Barricarte, Aurelio, Key, Timothy J, Trichopoulou, Antonia, Tsironis, Christo, Lagiou, Pagona, Masala, Giovanna, Pala, Valeria, Tumino, Rosario, Vineis, Paolo, Panico, Salvatore, Bueno de Mesquita, H. Ba, Siersema, Peter D, Ohlsson, Bodil, Jirström, Karin, Wennberg, Maria, Nilsson, Lena M, Weiderpass, Elisabete, Kühn, Tilman, Katzke, Verena, Khaw, Kay Tee, Wareham, Nick J, Tjønneland, Anne, Boeing, Heiner, Quirós, José R, Gunter, Marc J, Riboli, Elio, Norat, Teresa, Department of Medical and Clinical Genetics, Medicum, BMC, BMC, Department of Epidemiology and Public Health, Imperial College London, Instituto de Investigación Sanitaria de Palma (IdISPa), Hospital Universitario Son Espases, CIBER Fisiopatología de la Obesidad y Nutrición ( (CIBEROBN)), Instituto de Salud Carlos III [Madrid] (ISC), Department of Primary Care and Public Health, Department of Epidemiology, University Medical Center [Utrecht]-Julius Center for Health Sciences and Primary Care, Nutrition and Metabolism Section, International Agency for Cancer Research (IACR), Emory University [Atlanta, GA]-Rollins School of Public Health-Winship Cancer Institute, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Section for Epidemiology, Aarhus University [Aarhus], Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology (ICO-IDIBELL)-Cancer Epidemiology Research Programme, Granada Cancer Registry, Andalusian School of Public Health [Granada], Consorcio de Investigación Biomédica en Red especializado en Epidemiología y Salud Pública (CIBERESP), Los Centros de Investigación Biomédica en Red (CIBER), Murcia Regional Health Council [Murcia], Department of Health and Social Sciences, Universidad de Murcia, Navarre Public Health Institute, Cancer Epidemiology Unit, University of Oxford, Hellenic Health Foundation, Bureau of Epidemiologic Research, Academy of Athens, Department of Hygiene, Epidemiology and Medical Statistics, Harvard School of Public Health, Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute-ISPO, Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan], Cancer Registry and Histopathology Unit, Department of Oncology-Civile - M.P.Arezzo Hospital, Human Genetics Foundation (HuGeF), Università degli studi di Torino = University of Turin (UNITO), Dipartimento di Medicina Clinica e Chirurgia, University of Naples Federico II = Università degli studi di Napoli Federico II, Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya = Universiti Malaya [Kuala Lumpur, Malaisie] (UM), Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment [Bilthoven] (RIVM), Department of Gastroenterology and Hepatology, University Medical Center [Utrecht], Division of Internal Medicine, Skane University Hospital [Malmo], Lund University [Lund]-Lund University [Lund], Division of Oncology and Pathology, Lund University [Lund], Department of Public Health and Clinical Medicine, Nutritional Research, Umeå University, Arctic Research Centre, Department of Community Medicine, The Arctic University of Norway [Tromsø, Norway] (UiT), Department of Research, Cancer Registry of Norway, Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], Genetic Epidemiology Group [Helsinki], Folkhälsan Research Center, Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Division of Cancer Epidemiology, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Clinical Gerontology Unit, University of Cambridge [UK] (CAM), MRC Epidemiology Unit, University of Cambridge [UK] (CAM)-Institute of Metabolic Science, Danish Cancer Society Research Center, German Institute of Human Nutrition (DIfE) Potsdam-Rehbrücke, Public Health Directorate, Khaw, Kay-Tee [0000-0002-8802-2903], Wareham, Nicholas [0000-0003-1422-2993], Apollo - University of Cambridge Repository, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), University of Oxford [Oxford], Università degli studi di Torino (UNITO), University of Naples Federico II, University of Malaya, The Arctic University of Norway, University of Helsinki-University of Helsinki-Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki, [Romaguera,D, Ward,H, Vergnaud,A, Peeters,PH, Vineis,P, Bueno-de-Mesquita,HB, Gunter, MJ, Riboli,E, Norat,T] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. [Romaguera,D] Instituto de Investigación Sanitaria de Palma (IdISPa), Hospital Universitario Son Espases, Palma de Mallorca, Spain. [Romaguera,D] CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain. [Wark,PA] Global eHealth Unit, Department of Primary Care and Public Health, School of Public Health, Imperial College London, London, UK. [Peeters,PH, Gils, CH] Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. [Ferrari,P, Jenab,M] International Agency for Cancer Research (IARC), Lyon CEDEX, France. [Fedirko,V] Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, USA. [Fedirko,V] Winship Cancer Institute, Emory University, Atlanta, USA. [Boutron-Ruault,M, Dossus,L, Dartois,L] Inserm (Institut National de la Santé et de la Recherche Médicale), Centre for Research in Epidemiology and Population Health (CESP), Vaillant, Villejuif, Cedex, France. [Boutron-Ruault,M, Dartois,L] Univ Paris Sud, Villejuif, France. [Boutron-Ruault,M, Dartois,L] Gustave Roussy, Villejuif, France. [Hansen,CP, Dahm,CC] Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus C, Denmark. [Buckland,G] Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain. [Sánchez,MJ] Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs. GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain. [Sánchez,MJ, Dorronsoro,M, Navarro,C, Barricarte,A] CIBER de Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain. [Dorronsoro,M] Public Health Direction and Biodonostia Basque Regional Health Department, San Sebastian, Spain. [Navarro,C] Department of Epidemiology, Murcia Regional Health Council, Murcia, Spain. Department of Health and Social Sciences, Universidad de Murcia, Campus Universitario de Espinardo, Murcia, Spain. [Barricarte,A] Navarre Public Health Institute, Pamplona, Spain. [Key,TJ] Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford UK. [Trichopoulou,A, Tsironis,C] Hellenic Health Foundation, Athens, Greece . [Trichopoulou,A, Lagiou,P] Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. [Lagiou,P] Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece. [Lagiou,P] Department of Epidemiology, Harvard School of Public Health, Boston, USA. [Masala,G] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute – ISPO, Florence, Italy. [Pala,V] Epidemiology and Prevention Unit, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy. [Tumino,R] Cancer Registry and Histopathology Unit, 'Civic – M.P. Arezzo' Hospital, Ragusa, Italy. [Vineis,P] HuGeF Foundation, Turin, Italy. [Panico,S] Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy. [Bueno-de-Mesquita,HB] Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven The Netherlands. [Bueno-de-Mesquita,HB, Siersema,PD] Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands. [Bueno-de-Mesquita,HB] Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. [Ohlsson,B] Division of Internal Medicine, Department of Clinical Sciences, Skane University Hospital, Malmo, Lund University, Lund, Sweden. [Jirström,K] Department of Clinical Sciences, Division of Oncology and Pathology, Lund University, Lund, Sweden. [Wennberg,M] Public Health and Clinical Medicine, Nutritional Research, Umeå University, Umeå, Sweden. [Nilsson,LM] Arctic Research Centre, Umeå University, Umeå, Sweden. [Weiderpass,E] Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, ISM - Universitetet i Tromsø, Tromsø, Norway. Department of Research, Cancer Registry of Norway, Majorstuen Oslo, Norway. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Department of Genetic Epidemiology, Folkhälsan Research Center, Folkhälsan Research Center, Biomedicum 1, University of Helsinki, Helsinki, Finland. [Kühn,T, Katzke,V] German Cancer Research Center (DKFZ), Division of Cancer Epidemiology Im Neuenheimer Feld 581, Heidelberg, Germany. [Khaw,K] University of Cambridge School of Clinical Medicine, Clinical Gerontology Unit Box 251, Addenbrooke’s Hospital, Cambridge, UK. [Wareham,NJ] MRC Epidemiology Unit, University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK. [Tjønneland,A] Danish Cancer Society Research Center, Copenhagen, Denmark. [Boeing,H] Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany. [Quirós,JR] Public Health Directorate, Oviedo Asturias, Spain., This study was funded by the World Cancer Research Fund (WCRF) International Regular Grant Programme (Grant number 2009/44). Dora Romaguera holds a Ramon y Cajal contract (Ministerio de Economía y Competitividad, Spain and European Regional Development Fund, RYC-2011-08796). In addition, EPIC investigators acknowledge funding from the following agencies: Europe Against Cancer Program of the European Commission (SANCO), German Cancer Aid, German Cancer Research Center (DKFZ), German Federal Ministry of Education and Research (BMBF), Danish Cancer Society, Catalan Institute of Oncology, Spain, Health Research Fund (FIS) of the Spanish Ministry of Health, Spanish Regional Governments of Andalucía, Asturias, Basque Country, Murcia (no. 6236) and Navarra, ISCIII RCESP exp. C03/09 and ISCIII RETICC RD06/0020/0091, Spain, Cancer Research UK, Medical Research Council, United Kingdom, The Hellenic Health Foundation, Greece, Italian Association for Research on Cancer (AIRC), Italian National Research Council, Fondazione-Istituto Banco Napoli, Italy, Dutch Ministry of Public Health, Welfare and Sports, Dutch Prevention Funds, LK Research Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), The Netherlands, Swedish Cancer Society, Swedish Scientific Council, Regional Government of Skåne, Sweden, Helga—Nordic Center of Excellence Programme in Nutrition and Health, French League against Cancer (LNCC), National Institute for Health and Medical Research (INSERM), France, Mutuelle Générale de l'Education Romaguera et al. BMC Medicine (2015) 13:107 Page 10 of 12 Nationale (MGEN), France, 3 M Co., France, Gustave Roussy Institute (IGR), France, and and General Councils of France. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Subjects: Male, physical activity, 0302 clinical medicine, estudios prospectivos, Prospective Studies, estudios de cohortes, mediana edad, Aged, 80 and over, anciano, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Motor Activity [Medical Subject Headings], dieta, Incidence, Hazard ratio, COLON-CANCER, General Medicine, adulto, 3. Good health, Näringslära, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, estilo de vida, Cohort, Dieta, Estilo de Vida, RESEARCH FUND/AMERICAN INSTITUTE, Cohort study, Human, medicine.medical_specialty, Concordance, European Continental Ancestry Group, DIAGNOSIS, incidencia, White People, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Càncer colorectal, Neoplasias Colorrectales, BREAST-CANCER, Humans, Life Style, Aged, Cancer prevention, Proportional hazards model, Physical activity, Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms [Medical Subject Headings], Psychiatry and Psychology::Behavior and Behavior Mechanisms::Psychology, Social::Life Style [Medical Subject Headings], weight, LIFE-STYLE FACTORS, Colorectal cancer, REPRODUCTIVE HISTORY, Prospective Studie, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], Cancer and Oncology, Proportional Hazards Model, grupo de ascendencia continental europea, Estudios de Cohortes, Gerontology, cumplimiento del paciente, Survival, modelos de riesgos proporcionales, VDP::Medisinske Fag: 700::Helsefag: 800::Epidemiologi medisinsk og odontologisk statistikk: 803, [SDV]Life Sciences [q-bio], humanos, Colorectal Neoplasm, Alcohol consumption, Breast cancer, Prospective study, Named Groups::Persons::Survivors [Medical Subject Headings], Cohort Studies, 030212 general & internal medicine, Prospective cohort study, Non-U.S. Gov't, 2. Zero hunger, Medicine(all), RISK, Nutrition and Dietetics, Healthy lifestyle, Diet, Weight, Research Support, Non-U.S. Gov't, Public Health, Global Health, Social Medicine and Epidemiology, Middle Aged, European Prospective Investigation into Cancer and Nutrition, VDP::Medical disciplines: 700::Health sciences: 800::Epidemiology medical and dental statistics: 803, NUTRITION, Female, Colorectal Neoplasms, Research Article, Adult, neoplasias colorrectales, 3122 Cancers, RECREATIONAL PHYSICAL-ACTIVITY, Other Research Radboud Institute for Molecular Life Sciences [Radboudumc 0], colorectal cancer, Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet [Medical Subject Headings], Research Support, survival, Sobrevivientes, healthy lifestyle, Internal medicine, medicine, Journal Article, Proportional Hazards Models, Actividad Motora, business.industry, Physical fitness, BODY-MASS INDEX, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Other Clinical Medicine, 3121 General medicine, internal medicine and other clinical medicine, Patient Compliance, Cohort Studie, business, diet, Condició física
Abstract: Background: Cancer survivors are advised to follow lifestyle recommendations on diet, physical activity, and body fatness proposed by the World Cancer Research Fund/American Institute of Cancer Research (WCRF/AICR) for cancer prevention. Previous studies have demonstrated that higher concordance with these recommendations measured using an index score (the WCRF/AICR score) was associated with lower cancer incidence and mortality. The aim of this study was to evaluate the association between pre-diagnostic concordance with WCRF/AICR recommendations and mortality in colorectal cancer (CRC) patients. Methods: The association between the WCRF/AICR score (score range 0-6 in men and 0-7 in women; higher scores indicate greater concordance) assessed on average 6.4 years before diagnosis and CRC-specific (n = 872) and overall mortality (n = 1,113) was prospectively examined among 3,292 participants diagnosed with CRC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (mean follow-up time after diagnosis 4.2 years). Multivariable Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality. Results: The HRs (95% CIs) for CRC-specific mortality among participants in the second (score range in men/women: 2.25-2.75/3.25-3.75), third (3-3.75/4-4.75), and fourth (4-6/5-7) categories of the score were 0.87 (0.72-1.06), 0.74 (0.61-0.90), and 0.70 (0.56-0.89), respectively (P for trend, We would like to acknowledge the contribution of all participants in the study. This study was funded by the World Cancer Research Fund (WCRF) International Regular Grant Programme (Grant number 2009/44). Dora Romaguera holds a Ramon y Cajal contract (Ministerio de Economia y Competitividad, Spain and European Regional Development Fund; RYC-2011-08796). In addition, EPIC investigators acknowledge funding from the following agencies: Europe Against Cancer Program of the European Commission (SANCO); German Cancer Aid; German Cancer Research Center (DKFZ); German Federal Ministry of Education and Research (BMBF); Danish Cancer Society; Catalan Institute of Oncology, Spain; Health Research Fund (FIS) of the Spanish Ministry of Health; Spanish Regional Governments of Andalucia, Asturias, Basque Country, Murcia (no. 6236) and Navarra; ISCIII RCESP exp. C03/09 and ISCIII RETICC RD06/0020/0091, Spain; Cancer Research UK; Medical Research Council, United Kingdom; The Hellenic Health Foundation, Greece; Italian Association for Research on Cancer (AIRC); Italian National Research Council; Fondazione-Istituto Banco Napoli, Italy; Dutch Ministry of Public Health, Welfare and Sports, Dutch Prevention Funds, LK Research Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), The Netherlands; Swedish Cancer Society; Swedish Scientific Council; Regional Government of Skane, Sweden; Helga-Nordic Center of Excellence Programme in Nutrition and Health; French League against Cancer (LNCC); National Institute for Health and Medical Research (INSERM), France; Mutuelle Generale de l'Education Nationale (MGEN), France; 3 M Co., France; Gustave Roussy Institute (IGR), France; and General Councils of France.
Published: 2014
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19. mulPBA: an efficient multiple protein structure alignment method based on a structural alphabet

Author: Alexandre G. de Brevern, Sylvain Leonard, Agnel Praveen Joseph, Jean-Christophe Gelly, Narayanaswamy Srinivasan, Dynamique des Structures et Interactions des Macromolécules Biologiques (DSIMB), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), GR-Ex, Laboratoire d'Excellence, GR-Ex, Molecular Biophysics Unit, Indian Institute of Science, Indo-French collaborative grant (CEFIPRA/IFCPAR 3903-E) The Ministry of Research (France) The University Paris Diderot, Sorbonne Paris Cite (France) The National Institute of Blood Transfusion (INTS, France) The National Institute of Health and Medical Research (INSERM, France) The Laboratories of Excellence, GR-Ex (France) Department of Biotechnology (India), and de Brevern, Alexandre G.
Subjects: Models, Molecular, Web server, Protein Conformation, Computer science, Structural alignment, MESH: Sequence Alignment, computer.software_genre, webserver, 03 medical and health sciences, MESH: Software, MESH: Protein Conformation, Structural Biology, Iterative refinement, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Proteins, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Loop modeling, protein conformations, protein superimposition, Molecular Biology, Java applet, 030304 developmental biology, Internet, 0303 health sciences, Multiple sequence alignment, 030302 biochemistry & molecular biology, Computational Biology, Proteins, General Medicine, computer.file_format, Protein structure prediction, Protein Data Bank, Crystallography, MESH: Internet, protein structures, Protein Blocks, structural alphabet, Sequence Alignment, computer, Algorithm, Software, MESH: Models, Molecular, MESH: Computational Biology
Abstract: International audience; The increasing number of available protein structures requires efficient tools for multiple structure comparison. Indeed, multiple structural alignments are essential for the analysis of function, evolution and architecture of protein structures. For this purpose, we proposed a new web server called multiple Protein Block Alignment (mulPBA). This server implements a method based on a structural alphabet to describe the backbone conformation of a protein chain in terms of dihedral angles. This 'sequence-like' representation enables the use of powerful sequence alignment methods for primary structure comparison, followed by an iterative refinement of the structural superposition. This approach yields alignments superior to most of the rigid-body alignment methods and highly comparable with the flexible structure comparison approaches. We implement this method in a web server designed to do multiple structure superimpositions from a set of structures given by the user. Outputs are given as both sequence alignment and superposed 3D structures visualized directly by static images generated by PyMol or through a Jmol applet allowing dynamic interaction. Multiple global quality measures are given. Relatedness between structures is indicated by a distance dendogram. Superimposed structures in PDB format can be also downloaded, and the results are quickly obtained. mulPBA server can be accessed at www.dsimb.inserm.fr/dsimb_tools/mulpba/ .
Published: 2014
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20. β-Bulges: extensive structural analyses of β-sheets irregularities

Author: Craveur, Pierrick, Joseph, Agnel Praveen, Rebehmed, Joseph, De Brevern, Alexandre, GR-Ex, Laboratoire d'Excellence, GR-Ex, Dynamique des Structures et Interactions des Macromolécules Biologiques (DSIMB), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), National Centre for Biological Sciences [TIFR] (NCBS), Tata Institute for Fundamental Research (TIFR), The Ministry of Research (France), The University Paris Diderot, Sorbonne Paris Cite (France), The National Institute of Blood Transfusion (INTS, France), The National Institute of Health and Medical Research (INSERM, France), The Laboratories of Excellence, GR-Ex (France), HFSP (India), NCBS (India), and de Brevern, Alexandre G.
Subjects: [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Protein Conformation, Molecular Sequence Data, Proteins, Hydrogen Bonding, Articles, bioinformatics, Molecular Dynamics Simulation, sequence, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Protein Structure, Secondary, protein aggregation, Evolution, Molecular, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Amino Acid Sequence, Amino Acids, protein structure, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], structure relationship, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM]
Abstract: International audience; β-Sheets are quite frequent in protein structures and are stabilized by regular main-chain hydrogen bond patterns. Irregularities in β-sheets, named β-bulges, are distorted regions between two consecutive hydrogen bonds. They disrupt the classical alternation of side chain direction and can alter the directionality of β-strands. They are implicated in protein-protein interactions and are introduced to avoid β-strand aggregation. Five different types of β-bulges are defined. Previous studies on β-bulges were performed on a limited number of protein structures or one specific family. These studies evoked a potential conservation during evolution. In this work, we analyze the β-bulge distribution and conservation in terms of local backbone conformations and amino acid composition. Our dataset consists of 66 times more β-bulges than the last systematic study (Chan et al. Protein Science 1993, 2:1574-1590). Novel amino acid preferences are underlined and local structure conformations are highlighted by the use of a structural alphabet. We observed that β-bulges are preferably localized at the N- and C-termini of β-strands, but contrary to the earlier studies, no significant conservation of β-bulges was observed among structural homologues. Displacement of β-bulges along the sequence was also investigated by Molecular Dynamics simulations.
Published: 2013
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21. Evolution study of the Baeyer-Villiger monooxygenases enzyme family: functional importance of the highly conserved residues

Author: Véronique de Berardinis, Véronique Alphand, Alexandre G. de Brevern, Joseph Rebehmed, GR-Ex, Laboratoire d'Excellence, GR-Ex, Dynamique des Structures et Interactions des Macromolécules Biologiques (DSIMB), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA), Institut des Sciences Moléculaires de Marseille (ISM2), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC), Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), The Ministry of Research (France) The University Paris Diderot, Sorbonne Paris Cite (France) The National Institute of Blood Transfusion (INTS, France) The National Institute of Health and Medical Research (INSERM, France) The Laboratories of Excellence, GR-Ex (France) The National Center for Atomic Research (CEA,France) University d'Aix-Marseille (France) The National Center for Scientific Research (CNRS,France) high performance computing (HPC) resources at the French National Computing Center CINES under grant no. 2012-c2012076930 funded by the GENCI (Grand Equipement National de Calcul Intensif)., Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Génomique métabolique (UMR 8030), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), and de Brevern, Alexandre G.
Subjects: Threonine, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, ketones, phylogeny, 01 natural sciences, Biochemistry, Conserved sequence, Mixed Function Oxygenases, Protein structure, esters, Rhodococcus, [INFO.INFO-BT]Computer Science [cs]/Biotechnology, lactones, Conserved Sequence, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM], chemistry.chemical_classification, 0303 health sciences, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], [CHIM.ORGA]Chemical Sciences/Organic chemistry, enentioselectivity, [CHIM.CATA] Chemical Sciences/Catalysis, General Medicine, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Amino acid, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, [SDV.TOX] Life Sciences [q-bio]/Toxicology, [SDV.TOX]Life Sciences [q-bio]/Toxicology, sequence alignment, Flavin-Adenine Dinucleotide, Stereochemistry, Sequence alignment, Biology, 010402 general chemistry, stereoselectivity, 03 medical and health sciences, Pseudomonas, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, protein structure, 030304 developmental biology, function, Binding Sites, [CHIM.CATA]Chemical Sciences/Catalysis, Monooxygenase, interactions, [CHIM.ORGA] Chemical Sciences/Organic chemistry, 0104 chemical sciences, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, Enzyme binding, [INFO.INFO-BT] Computer Science [cs]/Biotechnology, chemistry, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Function (biology), NADP
Abstract: International audience; Baeyer-Villiger monooxygenases (BVMOs) catalyze the transformation of linear and cyclic ketones into their corresponding esters and lactones by introducing an oxygen atom into a C-C bond. This bioreaction has numerous advantages compared to its chemical version; it does not induce the use of potentially harmful reagents (i.e., green chemistry) and displays significant better enantio- and regio-selectivity. New potential BVMOs were searched using sequence homology for type I BVMO proteins. 116 new sequences were identified as new putative BVMOs respecting the defined selection criteria. Multiple sequence alignments were carried out on the selected sequences to study the conservation of structurally and/or functionally important amino acids during evolution. Type I BVMO signature motif was found to be conserved in 94.8% of the sequences. We noticed also the highly conserved - but previously unnoticed - Threonine 167 (93.1%), located in the signature motif; this position could be added in the pattern used to characterize specific Type I enzymes. Amino acids at the vicinity of the FAD and NADPH cofactors were found also to be highly conserved and the details of the interactions were emphasized. Interestingly, residues at the enzyme binding site were found less conserved in terms of sequence evolution, leading sometimes to some important amino acid changes. These behaviors could explain the enzyme selectivity and specificity for different ligands.
Published: 2013
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22. VLDP web server: a powerful geometric tool for analysing protein structures in their environment

Author: Alexandre G. de Brevern, Jeremy Esque, Sylvain Leonard, Christophe Oguey, Laboratoire de Physique Théorique et Modélisation (LPTM - UMR 8089), Centre National de la Recherche Scientifique (CNRS)-CY Cergy Paris Université (CY), GR-Ex, Laboratoire d'Excellence, GR-Ex, Dynamique des Structures et Interactions des Macromolécules Biologiques (DSIMB), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), The Ministry of Research (France) The University Paris Diderot, Sorbonne Paris Cite (France) The National Institute of Blood Transfusion (INTS, France) The National Institute of Health and Medical Research (INSERM, France) The Laboratories of Excellence, GR-Ex (France) The University of Cergy-Pontoise (France) The National Center for Scientific Research (CNRS,France), de Brevern, Alexandre G., and Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)
Subjects: Models, Molecular, Web server, MESH: Amino Acids, Protein Conformation, Voronoi, protein accessibility, Biology, Bioinformatics, computer.software_genre, 01 natural sciences, tessellations, Set (abstract data type), 03 medical and health sciences, MESH: Software, Protein structure, MESH: Protein Conformation, 0103 physical sciences, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Genetics, MESH: Proteins, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM], 030304 developmental biology, Delaunay, Internet, 0303 health sciences, amino acids, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Tessellation, 010304 chemical physics, Delaunay triangulation, Proteins, Articles, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Visualization, MESH: Internet, protein structures, Laguerre polynomials, protein volume, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Voronoi diagram, computer, Algorithm, Software, MESH: Models, Molecular
Abstract: International audience; Protein structures are an ensemble of atoms determined experimentally mostly by X-ray crystallography or Nuclear Magnetic Resonance. Studying 3D protein structures is a key point for better understanding protein function at a molecular level. We propose a set of accurate tools, for analysing protein structures, based on the reliable method of Voronoi-Laguerre tessellations. The Voronoi Laguerre Delaunay Protein web server (VLDPws) computes the Laguerre tessellation on a whole given system first embedded in solvent. Through this fine description, VLDPws gives the following data: (i) Amino acid volumes evaluated with high precision, as confirmed by good correlations with experimental data. (ii) A novel definition of inter-residue contacts within the given protein. (iii) A measure of the residue exposure to solvent that significantly improves the standard notion of accessibility in some cases. At present, no equivalent web server is available. VLDPws provides output in two complementary forms: direct visualization of the Laguerre tessellation, mostly its polygonal molecular surfaces; files of volumes; and areas, contacts and similar data for each residue and each atom. These files are available for download for further analysis. VLDPws can be accessed at http://www.dsimb.inserm.fr/dsimb_tools/vldp.
Published: 2013
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23. Cis-trans isomerization of omega dihedrals in proteins

Author: Pierrick Craveur, Pierre Poulain, Joseph Rebehmed, Agnel Praveen Joseph, Alexandre G. de Brevern, de Brevern, Alexandre G., GR-Ex, Laboratoire d'Excellence, GR-Ex, Dynamique des Structures et Interactions des Macromolécules Biologiques (DSIMB), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA), National Centre for Biological Sciences [TIFR] (NCBS), Tata Institute for Fundamental Research (TIFR), The Ministry of Research (France) The University Paris Diderot, Sorbonne Paris Cite (France) The National Institute of Blood Transfusion (INTS, France) The National Institute of Health and Medical Research (INSERM, France) The Laboratories of Excellence, GR-Ex (France) HFSP (India), and Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Models, Molecular, cis-trans-Isomerases, Protein Folding, Stereochemistry, Protein Conformation, MESH: Protein Folding, Clinical Biochemistry, Dihedral angle, Molecular Dynamics Simulation, 010402 general chemistry, Crystallography, X-Ray, 01 natural sciences, Biochemistry, iPBA, 03 medical and health sciences, Molecular dynamics, Protein structure, MESH: Protein Conformation, MESH: Protein Stability, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Peptide bond, Humans, MESH: Molecular Dynamics Simulation, MESH: Proteins, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, protein superimposition, 030304 developmental biology, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM], 0303 health sciences, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], MESH: Humans, Chemistry, Protein Stability, Organic Chemistry, Proteins, Protein structure prediction, protein function, MESH: Crystallography, X-Ray, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Cis trans isomerization, 0104 chemical sciences, protein structures, Protein folding, structural alphabet, isomerisation, MESH: cis-trans-Isomerases, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Isomerization, MESH: Models, Molecular
Abstract: International audience; Peptide bonds in protein structures are mainly found in trans conformation with a torsion angle ω close to 180°. Only a very low proportion is observed in cis conformation with ω angle around 0°. Cis-trans isomerization leads to local conformation changes which play an important role in many biological processes. In this paper, we reviewed the recent discoveries and research achievements in this field. First, we presented some interesting cases of biological processes in which cis-trans isomerization is directly implicated. It is involved in protein folding and various aspect of protein function like dimerization interfaces, autoinhibition control, channel gating, membrane binding. Then we reviewed conservation studies of cis peptide bonds which emphasized evolution constraints in term of sequence and local conformation. Finally we made an overview of the numerous molecular dynamics studies and prediction methodologies already developed to take into account this structural feature in the research area of protein modeling. Many cis peptide bonds have not been recognized as such due to the limited resolution of the data and to the refinement protocol used. Cis-trans proline isomerization reactions represents a vast and promising research area that still needs to be further explored for a better understanding of isomerization mechanism and improvement of cis peptide bond predictions.
Published: 2013
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24. Meat consumption and mortality--results from the European Prospective Investigation into Cancer and Nutrition

Author: Pietro Ferrari, Dagrun Engeset, Timothy J. Key, Kuanrong Li, Anne Tjønneland, Kim Overvad, José María Huerta, H. Bas Bueno-de-Mesquita, Christine L. Parr, Guri Skeie, Pilar Amiano, Kay-Tee Khaw, Teresa Norat, Göran Hallmans, Anne C. Vergnaud, Isabelle Romieux, Fulvio Ricceri, M. Luisa Redondo, Dimitirios Trichopoulos, Rosario Tumino, Veronika Fedirko, Françoise Clavel-Chapelon, Elio Riboli, Androniki Naska, Rikke Egeberg, Nicholas J. Wareham, Marianne Uhre Jakobsen, Emily Sonestedt, Heiner Boeing, Aurelio Barricarte, Salvatore Panico, Max Leenders, Manuela M. Bergmann, Laura Nailler, Isabel Drake, Paula Jakszyn, Marie-Christine Boutron-Ruault, Domenico Palli, Sabine Rohrmann, Vittorio Krogh, Antonia Trichopoulou, María José Sánchez, Jakob Linseisen, Petra H.M. Peeters, Ingegerd Johansson, Francesca L. Crowe, Rudolf Kaaks, Khaw, Kay-Tee [0000-0002-8802-2903], Wareham, Nicholas [0000-0003-1422-2993], Apollo - University of Cambridge Repository, University of Zurich, Rohrmann, Sabine, [Rohrmann,S] Division of Cancer Epidemiology and Prevention, Institute of Social and Preventive Medicine, University of Zurich, Zurich, Switzerland. [Rohrmann,S., Li,K, Kaaks,R, Linseisen,J] Division of Cancer Epidemiology, Deutsches Krebsforschungszentrum, Heidelberg, Germany. [Overvad,K, Jakobsen,MU] Section of Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark. [Bueno-de-Mesquita,HB] National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.[Bueno-de-Mesquita, HB, Leenders,M] Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands. [Egeberg,R, Tjønneland,A] Danish Cancer Society Research Center, Copenhagen, Denmark. [Nailler,L, Boutron-Ruault,MC, Clavel-Chapelon,F] Inserm, Centre for Research in Epidemiology and Population Health, Institut Gustave Roussy, Villejuif, France. [Nailler,L, Clavel-Chapelon,F] Paris South University, UMRS, Villejuif, France. [Krogh,V] Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy. [Palli,D] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Florence, Italy. [Panico,S] Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy. [Tumino,R] Cancer Registry and Histopathology Unit, 'Civile - M.P.Arezzo' Hospital, Ragusa, Italy. [Ricceri,F] HuGeF - Human Genetics Foundation - Torino, Torino, Italy. [Bergmann,MM, Boeing,H] Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany. [Khaw,KT] Department of Public Health and Primary Care, University of Cambridge, Cambridge UK. [Wareham,NJ] Medical Research Council (MRC) Epidemiology Unit, Cambridge UK. [Crowe,FL, Key,TJ] Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK. [Naska,A, Trichopoulou,A] WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece. [Trichopoulou,A, Trichopoulos,D] Hellenic Health Foundation, Athens, Greece. [Trichopoulos,D] Department of Epidemiology, Harvard School of Public Health, Boston MA, USA.Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. [Peeters,PHM] Julius Center, University Medical Center Utrecht, Utrecht, The Netherlands. [Peeters,PHM, Norat,T, Vergnaud,AC, Riboli,E] School of Public Health, Imperial College, London, UK. [Engeset,D, Skeie,G] Department of Community Medicine, University of Tromsø, Tromsø, Norway. [Parr,CL] Department of Biostatistics, Faculty of Medicine, University of Oslo, Oslo, Norway. [Jakszyn,P] Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), Barcelona, Spain. [Sánchez,MJ, Huerta,JM] Andalusian School of Public Health, Granada, Spain. [Sánchez,MJ, Barricarte,A, Amiano,P] Consortium for Biomedical Research in Epidemiology and Public Health (CIBER Epidemiología y Salud Pública-CIBERESP), Spain. [Huerta,JM] Department of Epidemiology, Murcia Regional Health Council, Murcia, Spain. [Redondo,ML] Public Health Directorate Asturias, Oviedo, Spain. [Barricarte,A] Navarre Public Health Institute, Pamplona, Spain. [Amiano,P] Public Health Division of Gipuzkoa, BIODonostia Research Institute, Department of Health of the Regional Government of the Basque Country, San Sebastian, Spain. [Drake,I, Sonestedt,E] Department of Clinical Sciences, Lund University, Malmö, Sweden. [Hallmans,G] Department of Public Health and Clinical Medicine, Nutrition Research, Umeå University, Umeå, Sweden. [Johansson,I] Department of Odontology, Cariology, Umeå University, Umeå, Sweden. [Fedirko,V, Romieux,I, Ferrari,P] International Agency for Research on Cancer (IARC), Lyon, France. [Linseisen,J] Institute of Epidemiology, Helmholtz Centre Munich, Neuherberg, Germany., Europe Against Cancer Program of the European Commission (SANCO), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum, German Federal Ministry of Education and Research, Danish Cancer Society, Health Research Fund (FIS) of the Spanish Ministry of Health, Spanish Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, ISCIII RCESP exp. C03/09, Spain, Cancer Research UK, Medical Research Council, United Kingdom, Stroke Association, United Kingdom, British Heart Foundation, Department of Health, United Kingdom, Food Standards Agency, United Kingdom, Wellcome Trust, United Kingdom, the Hellenic Health Foundation and the Stavros Niarchos Foundation, Italian Association for Research on Cancer (AIRC), Italian National Research Council, Fondazione-Istituto Banco Napoli, Italy, Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), Swedish Cancer Society, Swedish Scientific Council, Regional Government of Skåne, Sweden, Nordforsk the Norwegian Cancer Society, French League against Cancer (LNCC), National Institute for Health and Medical Research (INSERM), France, Mutuelle Générale de l’Education Nationale (MGEN), France, 3M Co, France, Gustave Roussy Institute (IGR), France, and General Councils of France, BMC, Ed., Division of Cancer Epidemiology and Prevention, Universität Zürich [Zürich] = University of Zurich (UZH)-Institute of Social and Preventive Medicine, Division of Cancer Epidemiology, Deutsches Krebsforschungszentrum, Section of Epidemiology, Aarhus University [Aarhus], Department of Gastroenterology and Hepatology, University Medical Centre, National Institute for Public Health and the Environment [Bilthoven] (RIVM), Danish Cancer Society Research Center, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan], Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Department of Clinical and Experimental Medicine, University of Naples Federico II = Università degli studi di Napoli Federico II, Cancer Registry and Histopathology Unit, Civile - M.P.Arezzo Hospital, HuGeF - Human Genetics Foundation - Torino, Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), Department of Public Health and Primary Care, University of Cambridge [UK] (CAM), Epidemiology Unit, Medical Research Council, Cancer Epidemiology Unit, University of Oxford, WHO Collaborating Center for Food and Nutrition Policies, University of Athens Medical School [Athens], Hellenic Health Foundation, Harvard School of Public Health, Bureau of Epidemiologic Research, Academy of Athens, Julius Center, University Medical Center [Utrecht], School of Public Health, Imperial College London, Department of Community Medicine, University of Tromsø (UiT), Department of Biostatistics [Oslo], Institute of Basic Medical Sciences [Oslo], Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO)-Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO), Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology (ICO), Andalusian School of Public Health [Granada], Consortium for Biomedical Research in Epidemiology and Public Health, CIBER de Epidemiología y Salud Pública (CIBERESP), Murcia Regional Health Council, Public Health Directorate Asturias, Navarre Public Health Institute, Public Health Division of Gipuzkoa, BIODonostia Research Institute, Department of Clinical Sciences, Lund University [Lund], Department of Public Health and Clinical Medicine, Umeå University, Department of Odontology, Cariology, International Agency for Cancer Research (IACR), Institute of Epidemiology, Helmholtz Centre Munich, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Università degli studi di Napoli Federico II, University of Oxford [Oxford], Rohrmann, S, Overvad, K, Bueno de Mesquita, Hb, Jakobsen, Mu, Egeberg, R, Tj?nneland, A, Nailler, L, Boutron Ruault, Mc, Clavel Chapelon, F, Krogh, V, Palli, D, Panico, Salvatore, Tumino, R, Ricceri, F, Bergmann, Mm, Boeing, H, Li, K, Kaaks, R, Khaw, Kt, Wareham, Nj, Crowe, Fl, Key, Tj, Naska, A, Trichopoulou, A, Trichopoulos, D, Leenders, M, Peeters, Ph, Engeset, D, Parr, Cl, Skeie, G, Jakszyn, P, S?nchez, Mj, Huerta, Jm, Redondo, Ml, Barricarte, A, Amiano, P, Drake, I, Sonestedt, E, Hallmans, G, Johansson, I, Fedirko, V, Romieux, I, Ferrari, P, Norat, T, Vergnaud, Ac, Riboli, E, and Linseisen, J.
Subjects: Male, 030309 nutrition & dietetics, Colorectal cancer, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Survival Analysis [Medical Subject Headings], Review, Named Groups::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], 2700 General Medicine, DISEASE, COLORECTAL-CANCER, VDP::Medical disciplines: 700::Health sciences: 800::Nutrition: 811, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Cohort Studies, Diet, Meat, Mortality, Cohort, Europe, Cardiovascular, Cancer, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Health Surveys::Nutrition Surveys [Medical Subject Headings], 0302 clinical medicine, Neoplasms, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, Medicine(all), RISK, CALIBRATION, 2. Zero hunger, 0303 health sciences, Nutrition and Dietetics, cardiovascular, Diabetes, Hazard ratio, food and beverages, cohort, General Medicine, Diseases::Neoplasms [Medical Subject Headings], Middle Aged, Nutrition Surveys, Neoplasias, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Näringslära, Cardiovascular Diseases, Red meat, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Female, Enfermedades cardiovasculares, Life Sciences & Biomedicine, Geographicals::Geographic Locations::Americas::North America::United States [Medical Subject Headings], CERTIFICATES, Research Article, Cohort study, Technology, Industry, Agriculture::Food and Beverages::Food::Meat [Medical Subject Headings], Adult, medicine.medical_specialty, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies [Medical Subject Headings], Processed meat, Estudios de cohortes, Check Tags::Male [Medical Subject Headings], 610 Medicine & health, Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet [Medical Subject Headings], Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Feeding Behavior [Medical Subject Headings], VDP::Medisinske Fag: 700::Helsefag: 800::Ernæring: 811, VEGETARIANS, 03 medical and health sciences, Medicine, General & Internal, General & Internal Medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Named Groups::Persons::Age Groups::Adult [Medical Subject Headings], medicine, cancer, Humans, ddc:610, Named Groups::Persons::Age Groups::Adult::Aged [Medical Subject Headings], Diseases::Cardiovascular Diseases [Medical Subject Headings], Aged, Science & Technology, business.industry, VDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762, 10060 Epidemiology, Biostatistics and Prevention Institute (EBPI), Feeding Behavior, medicine.disease, mortality, Survival Analysis, United States, Surgery, VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Onkologi: 762, RED MEAT, Check Tags::Female [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], Commentary, 21-YEAR FOLLOW-UP, business, Body mass index, Demography
Abstract: Background Recently, some US cohorts have shown a moderate association between red and processed meat consumption and mortality supporting the results of previous studies among vegetarians. The aim of this study was to examine the association of red meat, processed meat, and poultry consumption with the risk of early death in the European Prospective Investigation into Cancer and Nutrition (EPIC). Methods Included in the analysis were 448,568 men and women without prevalent cancer, stroke, or myocardial infarction, and with complete information on diet, smoking, physical activity and body mass index, who were between 35 and 69 years old at baseline. Cox proportional hazards regression was used to examine the association of meat consumption with all-cause and cause-specific mortality. Results As of June 2009, 26,344 deaths were observed. After multivariate adjustment, a high consumption of red meat was related to higher all-cause mortality (hazard ratio (HR) = 1.14, 95% confidence interval (CI) 1.01 to 1.28, 160+ versus 10 to 19.9 g/day), and the association was stronger for processed meat (HR = 1.44, 95% CI 1.24 to 1.66, 160+ versus 10 to 19.9 g/day). After correction for measurement error, higher all-cause mortality remained significant only for processed meat (HR = 1.18, 95% CI 1.11 to 1.25, per 50 g/d). We estimated that 3.3% (95% CI 1.5% to 5.0%) of deaths could be prevented if all participants had a processed meat consumption of less than 20 g/day. Significant associations with processed meat intake were observed for cardiovascular diseases, cancer, and 'other causes of death'. The consumption of poultry was not related to all-cause mortality. Conclusions The results of our analysis support a moderate positive association between processed meat consumption and mortality, in particular due to cardiovascular diseases, but also to cancer.
Published: 2013
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25. DoSA: Database of Structural Alignments

Author: Alexandre G. de Brevern, Bernard Offmann, Garima Agarwal, Narayanaswamy Srinivasan, Mohammed Iftekhar, Swapnil Mahajan, Dynamique des Structures et Interactions des Macromolécules Biologiques - Pôle de La Réunion (DSIMB Réunion), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Molecular Biophysics Unit, Indian Institute of Science, GR-Ex, Laboratoire d'Excellence, GR-Ex, National Centre for Biological Sciences [TIFR] (NCBS), Tata Institute for Fundamental Research (TIFR), Unité de fonctionnalité et ingénierie de protéines (UFIP), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS), Dynamique des Structures et Interactions des Macromolécules Biologiques (DSIMB), MBU, Indian Institute of Science-Indian Institute of Science, Indo-French collaborative grant (CEFIPRA/IFCPAR 3903-E) The Ministry of Research (France) The University Paris Diderot, Sorbonne Paris Cite (France) The National Institute of Blood Transfusion (INTS, France) The National Institute of Health and Medical Research (INSERM, France) The Laboratories of Excellence, GR-Ex (France) The University of Nantes (France) Fonds Européen de Dévelopment Régional and Conseil Regional de La Réunion [20100079, Tiers: 144645] Department of Biotechnology (India), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA), and de Brevern, Alexandre G.
Subjects: Models, Molecular, PALI, substitution matrix, optimisation, Statistics as Topic, MESH: Amino Acid Sequence, Molecular Biophysics Unit, computer.software_genre, Protein structure, MESH: Proteins, Databases, Protein, Structural motif, database, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM], MESH: Structural Homology, Protein, 0303 health sciences, Protein function, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Database, 030302 biochemistry & molecular biology, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], CLUSTALW, Original Article, Structural alphabet, General Agricultural and Biological Sciences, MESH: Models, Molecular, Information Systems, MESH: Databases, Protein, Molecular Sequence Data, Biology, iPBA, General Biochemistry, Genetics and Molecular Biology, Substitution matrix, Access to Information, 03 medical and health sciences, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Amino Acid Sequence, protein structure, Spatial Orientations, MESH: Statistics as Topic, 030304 developmental biology, MESH: Molecular Sequence Data, Proteins, Protein superfamily, MESH: Access to Information, Functional integrity, Structural Homology, Protein, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], protein structure superimposition, computer
Abstract: International audience; Protein structure alignment is a crucial step in protein structure-function analysis. Despite the advances in protein structure alignment algorithms, some of the local conformationally similar regions are mislabeled as structurally variable regions (SVRs). These regions are not well superimposed because of differences in their spatial orientations. The Database of Structural Alignments (DoSA) addresses this gap in identification of local structural similarities obscured in global protein structural alignments by realigning SVRs using an algorithm based on protein blocks. A set of protein blocks is a structural alphabet that abstracts protein structures into 16 unique local structural motifs. DoSA provides unique information about 159,780 conformationally similar and 56,140 conformationally dissimilar SVRs in 74 705 pairwise structural alignments of homologous proteins. The information provided on conformationally similar and dissimilar SVRs can be helpful to model loop regions. It is also conceivable that conformationally similar SVRs with conserved residues could potentially contribute toward functional integrity of homologues, and hence identifying such SVRs could be helpful in understanding the structural basis of protein function. Database URL: http://bo-protscience.fr/dosa/
Published: 2013
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26. Processed and Unprocessed Red Meat Consumption and Incident Type 2 Diabetes Among French Women

Author: Martin Lajous, Marie-Christine Boutron-Ruaualt, Françoise Clavel-Chapelon, Blandine de Lauzon-Guillain, Guy Fagherazzi, Laura Tondeur, Harvard School of Public Health, National Institute of Public Health = Instituto Nacional de Salud Pública [Cuernavaca, Mexique] (INSP), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), This E3N cohort was performed with the financial support of the Mutuelle Générale de l’Education Nationale, European Community, French League Against Cancer, Gustave Roussy Institute, French Institute of Health and Medical Research, and several general councils in France. The validation of potential diabetes cases was supported by the European Union (Integrated Project LSHM-CT-2006-037197 in Framework Program 6 of the European Community) InterAct project. The present analysis was conducted thanks to the International Associated Laboratory in Nutrition, Hormones, and Chronic Disease in Women, an ongoing collaboration between the National Institute of Health and Medical Research (INSERM, France) and the National Institute of Public Health (INSP, Mexico). M.L. was supported by the National Council for Science and Technology (Mexico), the INSP, the Ministry of Health (Mexico), the Department of Epidemiology at the Harvard School of Public Health, and the Bernard Lown Fund for Cardiovascular Health in the Developing World. G.F. was funded by the French Ministry of Research., TONDEUR, LAURA, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)
Subjects: MESH: Meat Products, Calorie, 030309 nutrition & dietetics, Endocrinology, Diabetes and Metabolism, Type 2 diabetes, Cohort Studies, 0302 clinical medicine, Surveys and Questionnaires, Prospective Studies, MESH: Incidence, Prospective cohort study, MESH: Cohort Studies, Original Research, 2. Zero hunger, MESH: Meat, 0303 health sciences, MESH: Middle Aged, Incidence, Middle Aged, 3. Good health, Menopause, Meat Products, Red Meat Consumption, Red meat, MESH: Feeding Behavior, Female, France, Cohort study, MESH: Diabetes Mellitus, Type 2, medicine.medical_specialty, Meat, 030209 endocrinology & metabolism, 03 medical and health sciences, Environmental health, Diabetes mellitus, Internal Medicine, medicine, Humans, Epidemiology/Health Services Research, MESH: Surveys and Questionnaires, Advanced and Specialized Nursing, MESH: Humans, business.industry, Feeding Behavior, medicine.disease, MESH: Prospective Studies, Surgery, MESH: France, Diabetes Mellitus, Type 2, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH: Female
Abstract: OBJECTIVE To evaluate the relation of processed and unprocessed red meat and incident type 2 diabetes. RESEARCH DESIGN AND METHODS We conducted a prospective study among 66,118 disease-free French women with dietary information from a validated questionnaire. Between 1993 and 2007, we identified 1,369 cases of incident diabetes. Multivariate analyses were adjusted for age, education, region, smoking, BMI, hypertension, hypercholesterolemia, physical activity, parental history of diabetes, menopause, hormone replacement therapy, alcohol, calories, n-3 fatty acids, carbohydrates, coffee, fiber, and fruits and vegetables. RESULTS Comparing the highest category of processed meat intake, ≥5 servings/week (median, 48 g/day), to the lowest, CONCLUSIONS In this large prospective cohort of French women, a direct association was observed only for processed red meat and type 2 diabetes.
Published: 2012
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27. Modeling and Molecular Dynamics of HPA-1a and -1b Polymorphisms: Effects on the Structure of the β3 Subunit of the αIIbβ3 Integrin

Author: Alexandre G. de Brevern, Pierre Poulain, Vincent Jallu, Patrick F.J. Fuchs, Cécile Kaplan, Laboratoire d'immunologie plaquettaire, Institut National de la Transfusion Sanguine [Paris] (INTS), GR-Ex, Laboratoire d'Excellence, GR-Ex, Dynamique des Structures et Interactions des Macromolécules Biologiques (DSIMB), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), The Ministry of Research (France) The University Paris Diderot, Sorbonne Paris Cite (France) The National Institute of Blood Transfusion (INTS, France) The National Institute of Health and Medical Research (INSERM, France) The Laboratories of Excellence, GR-Ex (France), de Brevern, Alexandre G., and Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, 030204 cardiovascular system & hematology, Molecular Dynamics, Epitope, MESH: Genotype, Epitopes, Computational Chemistry, 0302 clinical medicine, Protein structure, Genotype, MESH: Molecular Dynamics Simulation, Platelet, MESH: Models, Genetic, Immune Response, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM], MESH: Antigens, Human Platelet, Genetics, variants, 0303 health sciences, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Multidisciplinary, Integrin beta3, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Immunizations, MESH: Platelet Glycoprotein GPIIb-IIIa Complex, alloimmunisation, Platelet Glycoprotein GPIIb-IIIa Complex, Chemistry, Medicine, Research Article, Platelets, endocrine system, MESH: Epitopes, Science, Immunology, Integrin, Molecular Dynamics Simulation, Biology, 03 medical and health sciences, Antigen, MESH: Polymorphism, Genetic, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Antigens, Human Platelet, Allele, Alleles, 030304 developmental biology, Evolutionary Biology, MESH: Humans, Polymorphism, Genetic, Population Biology, Models, Genetic, Transfusion Medicine, MESH: Alleles, Immunity, Computational Biology, Thrombocytopenia, protein structures, Genetic Polymorphism, biology.protein, Clinical Immunology, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Population Genetics
Abstract: International audience; BACKGROUND: The HPA-1 alloimmune system carried by the platelet integrin αIIbβ3 is the primary cause of alloimmune thrombocytopenia in Caucasians and the HPA-1b allele might be a risk factor for thrombosis. HPA-1a and -1b alleles are defined by a leucine and a proline, respectively, at position 33 in the β3 subunit. Although the structure of αIIbβ3 is available, little is known about structural effects of the L33P substitution and its consequences on immune response and integrin functions. METHODOLOGY/PRINCIPAL FINDINGS: A complete 3D model of the L33-β3 extracellular domain was built and a P33 model was obtained by in silico mutagenesis. We then performed molecular dynamics simulations. Analyses focused on the PSI, I-EGF-1, and I-EGF-2 domains and confirmed higher exposure of residue 33 in the L33 β3 form. These analyses also showed major structural flexibility of all three domains in both forms, but increased flexibility in the P33 β3 form. The L33P substitution does not alter the local structure (residues 33 to 35) of the PSI domain, but modifies the structural equilibrium of the three domains. CONCLUSIONS: These results provide a better understanding of HPA-1 epitopes complexity and alloimmunization prevalence of HPA-1a. P33 gain of structure flexibility in the β3 knee may explain the increased adhesion capacity of HPA-1b platelets and the associated thrombotic risk. Our study provides important new insights into the relationship between HPA-1 variants and β3 structure that suggest possible effects on the alloimmune response and platelet function.
Published: 2012
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28. Therapeutic elevation of HDL-cholesterol to prevent atherosclerosis and coronary heart disease.

Author: Chapman MJ
Subjects: Amides, Animals, Biological Transport, Cholesterol metabolism, Cholesterol, HDL physiology, Esters, Homeostasis, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Inflammation prevention & control, Oxidative Stress, PPAR alpha agonists, PPAR delta agonists, PPAR gamma agonists, Quinolines therapeutic use, Sulfhydryl Compounds therapeutic use, Atherosclerosis prevention & control, Cholesterol, HDL blood, Coronary Disease prevention & control
Abstract: Innovative pharmacological approaches to raise anti-atherogenic high-density lipoprotein-cholesterol (HDL-C) are currently of considerable interest, particularly in atherogenic dyslipidemias characterized by low levels of HDL-C, such as type 2 diabetes, the metabolic syndrome, and mixed dyslipidemia, but equally among individuals with or at elevated risk for premature cardiovascular disease (CVD). Epidemiological and observational studies first demonstrated that HDL-C was a strong, independent predictor of coronary heart disease (CHD) risk, and suggested that raising HDL-C levels might afford clinical benefit. Accumulating data from clinical trials of pharmacological agents that raise HDL-C levels have supported this concept. In addition to the pivotal role that HDL-C plays in reverse cholesterol transport and cellular cholesterol efflux, HDL particles possess a spectrum of anti-inflammatory, anti-oxidative, anti-apoptotic, anti-thrombotic, vasodilatory and anti-infectious properties, all of which potentially contribute to their atheroprotective nature. Significantly, anti-atherogenic properties of HDL particles are attenuated in common metabolic diseases that are characterized by subnormal HDL-C levels, such as type 2 diabetes and metabolic syndrome. Inhibition of cholesteryl ester transfer protein (CETP), a key player in cholesterol metabolism and transport, constitutes an innovative target for HDL-C raising. In lipid efficacy trials, 2 CETP inhibitors-JTT-705 and torcetrapib-induced marked elevation in HDL-C levels, with torcetrapib displaying greater efficacy. Moreover, both agents attenuate aortic atherosclerosis in cholesterol-fed rabbits. Clinical trial data demonstrating the clinical benefits of these drugs on atherosclerosis and CHD are eagerly awaited.
Published: 2006
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28 results on '"National Institute for Health and Medical Research (INSERM), France"'

1. Dynamics and deformability of α-, 310- and π-helices

2. Structural variations within proteins can be as large as variations observed across their homologues

3. Analysis of Protein Disorder Predictions in the Light of a Protein Structural Alphabet

4. Discrete analysis of camelid variable domains: sequences, structures, and in-silico structure prediction: Sequence-structure characteristics of VHH domains

5. A structural entropy index to analyse local conformations in intrinsically disordered proteins: IDP PBs

6. VHH Structural Modelling Approaches: A Critical Review

7. Discrete analyses of protein dynamics

8. Investigation of the impact of PTMs on the protein backbone conformation

9. A minimum set of stable blocks for rational design of polypeptide chains Running head: A set of stable blocks for protein rational design

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11. A structural entropy index to analyse local conformations in intrinsically disordered proteins

12. Discrete analysis of camelid variable domains: sequences, structures, and in-silico structure prediction

13. In silico prediction of protein flexibility with local structure approach

14. Recent advances on polyproline II

15. Bioinformatic analysis of the protein/DNA interface

16. Understanding the role of domain–domain linkers in the spatial orientation of domains in multi-domain proteins

17. Trends in IT Innovation to Build a Next Generation Bioinformatics Solution to Manage and Analyse Biological Big Data Produced by NGS Technologies

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21. Evolution study of the Baeyer-Villiger monooxygenases enzyme family: functional importance of the highly conserved residues

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23. Cis-trans isomerization of omega dihedrals in proteins

24. Meat consumption and mortality--results from the European Prospective Investigation into Cancer and Nutrition

25. DoSA: Database of Structural Alignments

26. Processed and Unprocessed Red Meat Consumption and Incident Type 2 Diabetes Among French Women

27. Modeling and Molecular Dynamics of HPA-1a and -1b Polymorphisms: Effects on the Structure of the β3 Subunit of the αIIbβ3 Integrin

28. Therapeutic elevation of HDL-cholesterol to prevent atherosclerosis and coronary heart disease.

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28 results on '"National Institute for Health and Medical Research (INSERM), France"'

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