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Bio-informatique Structurale au Centre de Biochimie Structurale (Montpellier)

Bio-informatique Structurale au Centre de Biochimie Structurale (Montpellier). http://www.cbs.cnrs.fr. 22 Octobre 2003 . Programmes, serveurs Internet et bases de données du CBS : ViTO (Vincent Catherinot) : Optimisation & visualisation

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Bio-informatique Structurale au Centre de Biochimie Structurale (Montpellier)

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  1. Bio-informatique Structurale au Centre de Biochimie Structurale (Montpellier) http://www.cbs.cnrs.fr 22 Octobre 2003

  2. Programmes, serveurs Internet et bases de données du CBS : ViTO (Vincent Catherinot) : Optimisation & visualisation LEA-3D (Dominique Douguet) : Conception rationnelle de ligands RESCUE (Marc-André Delsuc) : Attribution RMN T.I.T.O. (Gilles Labesse) : Optimisation d’alignements structuraux E.Q.M. (Laetitia Martin) : Analyse structurale Bioserv (Dominique Douguet) : modélisation moléculaire Eval123D (Jean-Chrisophe Gely) : évaluation moléculaire Knottins (Laurent Chiche) : base de PPRPD DOMO 2 (Jerome Gracy) : base de domaines protéiques NMRb (Jean-Luc Pons) : base de spectres RMN

  3. Bioserv 1D (Genpept, ...) 3D (PDB, MSD) Reconnaissance de repliement meta-server alignements structuraux T.I.T.O.,ViTO Sélection,Optimisation alignement structural Modélisation SCWRL, MODELLER modèles tridimensionnels Evaluation PROSA, Verify3D, ERRAT, ViTO, EvTREE modèle tridimensionnel LEA-3D, FlexX, ViTO, Fitter RESCUE, Fireman Criblage virtuel, conception rationnelle de ligands Validation expérimentale remplacement moléculaire From molecular modelling to drug design. Cohen-Gonsaud, Catherinot, Labesse, Douguet. In Prog. Nucleic Acid Res. “Applied Bio-informatics“, Ed. Bujnicki, (2003) Springer-Verlag.

  4. 1cc8 : Identity ~37 % 1qup : Identity ~20 % 1afj : Identity ~22 % 1fxr : Identity ~12 %

  5. Edition et Visualisation : ViTO. V. Catherinot & G. Labesse, CBS SH3 Nef

  6. Applications de ViTO CggR : Identité 11 % Effecteur naturel Declercq et al., en préparation Ssu72 : Identité 15 % (5ptp) inhibiteur 10 µM Ganem et al., EMBO J. (2003) Cytokine bactérienne : Identité 28 % Activité enzymatique Cohen-gonsaud et al., TiBS (2004)

  7. Criblage in silico ViTO FlexX / LEA • Criblages effectués (~40000 molécules) : • (TMPK, PknA, B & D) • 1 ligand micromolaire (TMPK) • (7 molécules testées)

  8. BIOSERV http://bioserv.cbs.cnrs.fr Fifth Community Wide Experiment on the Critical Assessment of Techniques for Protein Structure Prediction Asilomar Conference Center December 1 - 5th, 2002 ~ 60 protéines à modéliser avec 3 à 50% d’identité de séquence avec des structures connues And the winners are ... the meta-servers !

  9. 100 20 80 IV 40 60 Le site KNOTTINES http://knottin.cbs.cnrs.fr • Les knottins : • Petites, stables, tolérantes aux variations de séquence, (inhibiteurs, toxines, antibactériens, hormones, …) • Plate-formes pour la conception d’inhibiteurs • Nomenclature et numérotation unique • Base de données séquences/structures (PHP/MySQL) • Recherches : mots-clés, séquences (BLAST/HMMER), motifs structuraux • Affichages : tableaux ordonnés,alignements de séquences

  10. EvDTree : apprentissage machine des relations séquence-structure • Classifications de structures locales par arbre de décision • Matrices de substitutions et potentiels statistiques dépendants de la structure 3D Eval123D : un meta-serveur d’évaluation de structures de protéines • Utilisation des méthodes les plus populaires (Verify3D, Eval2D, ProsaII, SFE) et une version préliminaire d’EvDTree • Métrique identique permettant la comparaison des différentes méthodes • Disponible à l’adresse : http://bioserv.cbs.cnrs.fr/valid.html

  11. Support d’évaluation des méthodes d'analyse automatique en RMN : La NMRb J.-L. Pons & M.-A. Delsuc, CBS Base de spectres RMN : . Spectres bruts . 14 laboratoires utilisateurs . Articulation avec PDB / BMRB http://nmrb.cbs.cnrs.fr Rescue Fireman

  12. Publications 2001-2003 • MOMP a divergent porin from Campylobacter jejuni cloning and primary structural characterization. Labesse, Garnotel, Bonnel, Dumas, Pagés & Bolla, B.B.R.C. (2001) 280, 380-7. • Thymidylate Kinase of Mycobacterium tuberculosis: A chimera sharing properties common to Eucaryotic and bacterial enzymes. Munier-Lehmann, Chaffotte, Pochet & Labesse. Prot. Science (2001) 10, 1195-205. • - Easier threading through Web-based comparisons and cross-validations. Douguet and Labesse. Bioinformatics. (2001) 17, 752-3. • - Biochemical characterization of the helper component of Cauliflower mosaic virus. Hébrard, Drucker, Leclerc, Hohn, Uzest, Froissart, Strub, Sanglier, Van Dorsselaer, Padilla, Labesse & Blanc. Virology. (2001) 75, 8538-46. • - From sequence to structure to function: a case study. Douguet, Bolla, Munier-Lehmann and Labesse. Enzyme and Microbiology Tech. (2002) 30, 289-294. • - Nucleoside Analogs as Inhibitors of Thymidylate Kinases: Possible Therapeutical Applications Pochet, Dugue, Douguet, Labesse & Munier-Lehmann, Chem. Bio. Chem. (2002), 1, 108-10. • - Biochemical and structural studies of the Mycobacterium tuberculosis MabA (FabG1) protein involved in the fatty acid elongation system, FAS-II. Marrakchi, Ducasse, Labesse, Margeat, Montrozier, Emorine, Charpentier, Lanéelle & Quémard. Microbiology. (2002) 148, 951-60. • - Diacylglyceride kinases, sphingosine kinases and NAD Kinases are related to 6-phosphofructokinases. Labesse, Douguet, Assairi & Gilles. TiBS. (2002) 27, 273-5. • - Comparative modelling and immunochemical studies of Escherichia coli UMP kinase. Labesse, Bucurenci, Douguet, Sakamoto, Landais, Gagyi, Gilles & Bârzu. B.B.R.C. (2002) 294, 173-9. • - Crystal structure of MabA from Mycobacterium tuberculosis, a reductase involved in long-chain fatty acid biosynthesis. Cohen-Gonsaud, Ducasse, Hoh, Zerbib, Labesse & Quémard. J. Mol. Biol.(2002) 320, 249-61. • - Ligand binding in the GB2 subunit of the GABAB heteromeric receptor is not required for receptor activation and allosteric interaction between the subunits. Kniazeff, Galvez, Labesse & Pin. J. Neurosci. (2002) 22, 7352-61. • - Structural and Ligand Binding Properties of YajQ and YnaF, two Proteins from Escherichia coli with Unknown Biological Function Saveanu, Miron, Borza, Craescu, Labesse, Gagyi, Popescu, Schaeffer, Namane, Laurent-Winter, Bârzu & Gilles. Protein Sci. (2002) 11, 2551-60. • - Ssu72 is a phosphatase essential for transcription termination of snoRNAs and specific mRNAs in yeast. Ganem, Devaux, Torchet, Jacq, Quevillon-Cheruel, Labesse, Facca & Faye. EMBO J. (2003), 22, 1588-98. • - Comparative sequence analysis and predictions for the envelope glycoproteins of insect endogenous retroviruses. Misseri, Labesse, Bucheton & Terzian. TiMS (2003). 11, 253-6. • - Comparative study of purine and pyrimidine nucleoside analogues acting on the Mycobacterium tuberculosis and human thymidylate kinases Pochet, Dugue, Labesse, Delepierre & Munier-Lehmann, Chem. Bio. Chem. (2003), 4, 742-7. • - UMP kinase from the gram-positive bacterium Bacillus subtilis is strongly dependent on GTP for optimal activity Gagyi, Sakamoto, Bucurenci, Labesse, Ionescu, Borza, Assairi, Laurent-Winter, Landais, Gounon, Rousselle, Danchin, Bârzu & Gilles, Eur. J. Biochem.(2003), 270, 3196-204. • - Molecular Recognition of Paxillin LD-motifs by the Focal Adhesion Targeting Domain. Hoellerer, Noble, Labesse, Werner, Campbell & Arold.Structure (2003). Sous presse. • Superposition of chemical shifts in NMR spectra can be overcome to determine automatically the structure of a proteinAuguin, Catherinot, Malliavin, Pons, Delsuc (2003), Spectroscopy17 559-68. • Refined solution structure of a liganded type 2 wheat nonspecific lipid transfer protein,Pons, de Lamotte, Gautier, Delsuc (2003) J Biol Chem278 14249-56 • Resuscitation promoting factors possess a lysozyme-like domain. Cohen-Gonsaud, Kepp, Davies, Ward, Henderson & Labesse. (2004),TiBS sous presse. • The KNOTTIN website and database: A new information system dedicated to the knottin scaffoldGelly, Gracy, Kaas, Le-Nguyen, Heitz, Chiche (2004),Nucleic Acids res. sous press

  13. Centre de Biochimie Structurale http://www.cbs.cnrs.fr V. Catherinot (CDD INSERM) FITTER,ViTO L. Chiche (DR CNRS) SFE, Knottins M.-A. Delsuc (DR CNRS)GifA D. Douguet (CR INSERM)BIOSERV, LEA-3D J.C. Gelly (Thèse) EVTREE J. Gracy (IR CNRS) DOMO 2 G. Labesse (CR CNRS) T.I.T.O. L. Martin (Thèse)E.Q.M. J.L. Pons (IR CNRS) RESCUE, NMRb

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