MiniTAGp 2011: Theoretical Approaches for the Genome and the proteins

LAPTh, Annecy-Le-Vieux

LAPTh, Annecy-Le-Vieux

9, Chemin de Bellevue - BP 110 - 74941 ANNECY-LE-VIEUX CEDEX
Claire Lesieur (LAPTh), Giovanni Feverati (LAPTh), Laurent Vuillon

From 12:00 of Thursday, the 15 of September, to 15:30 of Friday, the 16 of September

We are glad to present this short conference, MiniTagp2011, the fourth of a series of conferences TAG06, TAG08 and TAGp2010.
This event aims at bringing in contact people from different domains (physics, mathematics, biology, computer science) concerned with various theoretical and experimental aspects of the genome and of the structure of proteins. MiniTAGp2011 will focus on fundamental interactions in


The TAGp participants cover an extremely large spectrum of skills and expertises. They are interested and ready to listen, discover and share this huge variety of research fields. For the TAGp meeting to be successfull, we ask all the speakers to be particularly careful to the clarity of their presentations.

Confirmed speakers

1) Maria Barbi (Paris) Non-specific DNA-protein interaction: how proteins can diffuse along DNA
2) Frédéric Cazals (Nice) Assessing the stability of protein complexes within large assemblies
3) Michele Caselle (Torino) Quantitative biology
4) Giovanni Feverati (Annecy) Protein interfaces: a networking story
5) Alexander Grossmann (Marseille) Interactive reading of sequences
6) Joël Janin (Paris) Protein-protein interactions: modeling structure and affinity


There are no inscription fees to this conference. However, we need to know the number of participants so please register in the appropriate form not after Monday, the 12 of September 2011. Let us know in advance if you need to cancel your registration.

The Tuesday and Friday lunches will most probably be offered by the organization. The Tuesday evening we will have diner in a typical Annecy restaurant (payed to the speakers).

The conference language is english

The organizers

Giovanni Feverati, Claire Lesieur, Laurent Vuillon


CNRS LAPTh Université de savoie

  • Alexander Grossmann
  • Benjamin BOUVIER
  • Benjamin Clémençon
  • Boutet Emmanuel
  • Branko Dragovich
  • Claire Lesieur
  • Didier Verkindt
  • Frederic Cazals
  • Giovanni Feverati
  • Guillaume JAMES
  • Joel Janin
  • Laurent Vuillon
  • Maria barbi
  • Marie CUMENER
  • Michele Caselle
  • Paul Sorba
  • Sylvie RICARD-BLUM
  • Thierry CHAMPION
  • Thursday, 15 September
    • 12:00 13:00
      Interactive reading of sequences 1h
      This will be a presentation of a straightforward semi-graphical tool for exploring a family of sequences.
      Speaker: Alexander Grossmann
    • 13:00 14:30
      Lunch 1h 30m
    • 14:30 15:30
      Non-specific DNA-protein interaction: how proteins can diffuse along DNA 1h
      The structure of DNA binding proteins (DNA-BPs) enables a strong interaction with their specific target site on DNA through direct interactions with DNA base pairs. However, recent single molecule experiment reported that proteins can diffuse on DNA. Interactions between proteins and non-specific DNA should therefore play a crucial role during the target search. Nucleotides being negatively charged, the positive surface of DNA-BPs is expected to collapse onto DNA. This is indeed what is observed by means of Monte Carlo simulations for an oversimplified model of the system where the DNA is represented by a cylinder and the protein by a sphere. However, the most characteristic aspect of DNA-BPs is their shape complementarity with DNA [1]. We showed that, if the concave shape of DNA-BPs is taken into account, a counter-intuitive repulsion between the two oppositely charged macromolecules exists at a nanometer range [2,3], which pushes the protein in a free energy minimum at a distance from DNA. As a consequence, a favorable path exists along which proteins can slide without interacting with the DNA bases. When a protein encounters its target, the osmotic barrier is completely counter-balanced by the local H-bond interaction, thus enabling the sequence recognition. The implications of such a behavior on the protein 1D diffusion along DNA recently observed both in vitro and in vivo [4,5] will be the goal of future investigations. [1] S. Jones, P. van Heyningen, H.M. Berman, and J.M. Thornton Protein-DNA interactions: a structural analysis J. Mol. Biol., 287:877–896, 1999. [2] V. Dahirel, F. Paillusson, M. Jardat, M. Barbi, J-M. Victor Non-specific DNA-protein interaction: Why proteins can diffuse along DNA, Phys. Rev. Lett., in press (2009) -- arXiv:0902.2708. [3] F. Paillusson, M. Barbi, J-M. Victor Poisson-Boltzmann for oppositely charged bodies: an explicit derivation, Molecular Physics, in press (2009) -- arXiv:0902.1457. [4] J. Gorman, and E.C. Greene, Visualizing One-dimensional Diffusion of Proteins along DNA Nature Structural and Molecular Biology15:5752-5757 (2008). [5] J. Elf, G.W. Li, and X.S. Xie. Probing Transcription Factor Dynamics at the Single-Molecule Level in a Living Cell Science, 316:1191 – 1194, 2007.
      Speaker: Mrs Maria Barbi
    • 15:30 16:30
      Protein-protein interactions: modeling structure and affinity 1h
      The Protein Data Bank (PDB) illustrates many types of protein-protein interactions, specific in oligomeric proteins and in transient complexes, non-specific at crystal packing contacts. The information in it is geometric and chemical in nature, but it can also be interpreted in terms of the physics (thermodynamic stability and binding mechanisms) and the biology of the interaction (function, specificity, and evolution) [1-2]. Protein-protein docking methods yield structural models that a community-wide experiment (CAPRI, Critical Assessment of PRedicted Interactions, tests in blind predictions. In ten years of CAPRI, the prediction has succeeded on 70% of the targets, and most of the failures were due to major conformation changes accompanying the interaction. As conformation changes also govern affinity [4], the challenge is now to model protein flexibility and predict both the structure of the assembly and its thermodynamic stability. 1. Janin J, Bahadur RP, Chakrabarti P (2008). Protein-protein interaction and quaternary structure. Quart. Rev. Biophysics 41:133-180. 2. Dey S, Pal A, Chakrabarti P, Janin J. (2010). The subunit interfaces of weakly associated homodimeric proteins. J. Mol. Biol. 398:146-160. 3. Janin J (2010) Protein-protein docking tested in blind predictions: the CAPRI experiment. Mol. Biosystems 6, 2351–2362. 4. A structure-based benchmark for protein-protein binding affinity. Kastritis PL, Moal IH, Hwang H, Bonvin AMJJ, Bates PA, Weng Z, Janin J (2011) Protein Sci. 20:482—491.
      Speaker: Mr Joel Janin
    • 16:30 16:50
      Short discussion on interdisciplinarity 20m
  • Friday, 16 September
    • 09:00 09:20
      Archamps: The BioPark. Presentation by B. Holland and K. Arafah
    • 09:20 10:20
      Assessing the stability of protein complexes within large assemblies 1h
      Structural genomics projects exploiting Tandem Affinity Purification (TAP) or similar data have revealed remarkable features of proteomes [G06]. While these insights are essentially of combinatorial nature---selected proteins are known to interact within a complex, leveraging this information requires building three dimensional models of these complexes. Such an endeavour has recently been completed for the Nuclear Pore Complex (NPC), for which plausible reconstructions have been computed from different experimental data, including TAP data [A07a-b]. Yet, a full synergy between TAP data and the reconstruction is not at play for two reasons. First, the models built are qualitative. Second, the reconstruction does not elucidate the precise connexion between the model and TAP data. In particular, deciding whether proteins seen in a TAP experiment correspond to a single complex or a mixture of complexes within the NPC is not addressed. This talk will present a method addressing these limitations. First, we shall introduce toleranced models to inherently model uncertain shapes. A toleranced model is a one-parameter family of shapes (a continuum of geometries) representing an uncertain shape, which can be used to investigate stable complexes amidst the continuum. Second, for models reconstructed from TAP data, we shall explain how toleranced models and their built-in geometric statistics can be used to infer stable contacts, and also to investigate protein complexes associated to specific protein types. Illustrations will be provided on NPC models derived from the density maps presented in [A07a-b]. Bibliography [G06] A-C. Gavin et al; Nature, 440, 2006. [A07a-b] F. Alber and Al; Nature, 450, 2007. [CD10] F. Cazals and T. Dreyfus; Symposium on Geometry Processing, 2010; [CD11] F. Cazals and T. Dreyfus; INRIA Techreport 7513, 2011;
      Speaker: Frédéric Cazals
    • 10:20 10:40
      Coffee 20m
    • 10:40 11:40
      Protein Interfaces: a networking story 1h
      The assembly of subunits in protein oligomers is an important topic to study as a vast number of proteins exists as stable or transient oligomers. Only a few of the amino acids that constitute a protein oligomer seem to regulate the capacity of the protein to assemble (to form interfaces), and some of these amino acids are localized at the interfaces that link the different chains. We have developed a series of programs, under the common name of Gemini, that can select the subset of the residues that is involved in the interfaces of a protein oligomer, and generate a 2D interaction network (or graph) of the subset. We have used these programs to investigate interfaces made of two adjacent beta strands (one on each side of the interface). The graphs show a peculiar presence of two subnetworks, one of the backbone-backbone interactions and one with side chain interactions. A differential use of the amino acids emerges.
      Speaker: Giovanni Feverati (LAPTH)
    • 11:40 12:20
      A minimum principle in codon-anticodon interaction 40m
      Imposing a minimum principle in the framework of the so called crystal basis model of the genetic code, we determine the structure of the minimum set of 22 anticodons which allows the translation-transcription for animal mitochondrial code. The results are in very good agreement with the observed anticodons.
      Speaker: Paul Sorba
    • 12:20 14:00
      Lunch 1h 40m
    • 14:00 15:00
      Quantitative biology 1h
      The talk will be devoted to a general survey of the applications of the tools of theoretical physics to modern molecular biology. After a general introduction to modern genomics, to the sequencing projects and to the so called "Systems Biology" approach, I will discuss in more detail three examples: the role of evolution in shaping the genome, the network properties of gene regulation and the use of statistical mechanics tools to describe chemotaxis.
      Speaker: Michele Caselle (Università di Torino)