Robustness and plasticity of theoretical and biological networks

10 juin 2014, 09:00 → 12 juin 2014, 18:00 Europe/Paris

BioPark Archamps

Laurent VUILLON (LAMA), claire lesieur (LAPTH)

The shape and the function of proteins are based on the interactions between atoms of the amino acids, the basic unit making proteins. Most of the amino acids of a protein resist mutation as their modification do not lead to functional and/or conformational changes. Nevertheless, few of them are vulnerable to modifications which yield severe changes associated to diseases, functional changes, or evolution (Dan Tawfik). In the recent years, proteins have been described as amino acid interaction networks with amino acids and interactions as nodes and links, respectively (Claire Lesieur). It is therefore possible to investigate how proteins combine robustness and plasticity towards local changes using theoretical approaches such as network/graph theories.
Fortunately, the features and dynamics of theoretical, social and informatics networks are well studied by mathematics (Sylvain Séné), physics and computer science (Kave Salamatian). The goal of the meeting is to explore the robustness and the plasticity of non-biological networks to anticipate network measures most suitable to address structural, mechanical and functional changes in proteins.
In a complementary way, the workshop will explore alternative approaches investigating the mechanisms that enable local information to spread globally and yield complex structures: Molecular dynamics combined to graph theory (David Wales), tiling/symmetry (Laurent Vuillon, Pierre-Etienne Meunier), protein mechanical properties (Keqin Zhang) and protein pattern designs (Sylvie Ricard Blum).

The meeting is on three days, the mornings are dedicated to talks, the afternoons to discussion and the evening to food/walk/climbing. The Biopark is located in front of a rock climbing cliff, if anybody is interested, we can organize some easy climbs one evening (weather permitted), please let us know. We suggest you to bring some trainers for walking.

The organizers:
Claire Lesieur, Laurent Vuillon, Virginie Malaval


 

Avec la participation de:
    
 

Transparents

• Archamps_2014_LV.pdf
• ArchampsKV.pdf
• DJW.pdf
• LesieurC.pdf
• Ricard_Blum_Archamps_2014.pdf
• Robustness_and_innovability_of_protein_foldsnote.pdf
• Self-assembly-Meunier.pdf
• Senearchamps.pdf
• Silk_Archamps.pdf

mar. 10 juin

Dan TAWFIK / The robustness and innovability of protein folds

Dan S. Tawfik
Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, 76100, Israel
Over 60% of the known folds carry out one or two enzymatic functions, while few folds, e.g. the TIM-barrel and Rossmann folds, exhibit hundreds. Are there structural features that make a fold amenable to functional innovation (innovability)? Do these features relate to robustness – the ability to readily accumulate sequence changes? I will discuss several hypotheses regarding the relationship between the architecture of a protein and its evolutionary potential. I will describe how, in a seemingly paradoxical manner, opposite properties such as high stability and rigidity vs. conformational plasticity, and respectively, structural order vs. disorder, promote robustness and/or innovability. Indeed, polarity – differentiation and low connectivity between a protein’s scaffold and its active-site, is a key prerequisite for innovability.

Sylvain SENE / Interaction networks and their environment

Laboratoire d'informatique fondamentale, université de Marseille.
In this talk will be presented fundamental results which show formally that the environment of interaction networks plays a central role on their dynamical behaviours. Although an application to a biological network will be discussed, the focus will notably put on probabilistic cellular automata.

Kavé SALAMATIAN

12:45 LUNCH

Working session/discussion

mer. 11 juin

Pierre-Etienne Menier

Laurent VUILLON

Claire LESIEUR / Networks and Protein assembly

AGIM (Aging and Imaging), UGA-CNRS, Grenoble
Federation de recherche FR2914, MSIF (Modelisation, Simulation, Interactions Fondamentales)

Proteins are biological entities made of a chain of amino acids bound to one another in a specific sequence. Based on the sequence and the environment, the protein acquires a tridimensional shape called tertiary structure (3D-structure) suitable for its biological function. The vast majority of proteins are oligomers which assemble several copies of their chains in order to function. They either fold individual chains and subsequently associate them (lock and key mechanism) or fold and associate the chains concomitantly (fly-casting mechanism). The association of chains involves interactions between atoms of the amino acids of different chains to form a protein interface. Only some of the amino acids of the protein interface, so-called hot spots are regulating the association steps. In addition, there are some residues located outside the protein interface, often upstream, that regulate association [1, 2]. For example, a proline residue located upstream a protein interface domain changes the spatial position of the domain through a cis-trans isomerization and hence regulates the chain association [3]. The single modification of some of the amino acids of a protein is sufficient to (i) prevent assembly, (ii) modify assembly or (iii) change the route of assembly. At the same time, the mutation of most amino acids has no effect on the assembly. This implies that the protein combined fold/assembly robustness and fold/assembly plasticity through the regulation of local changes, namely single amino acid.
A network is a set of points (nodes) connected to one another by links. The strength of the network/graph theory is the capacity to yield information on the nodes, on the pairs of nodes (links) and on the dynamics of the network, ie the communication between nodes and more importantly beyond pairs of nodes.
We will discuss how such capacity is relevant to address protein fold robustness and plasticity [4, 5]
[1]. Csermely P. Creative elements: network-based predictions of active centres in proteins and cellular and social networks. Trends Biochem Sci. 2008 Dec;33(12):569-76. PubMed PMID: 18945619.
[2]. Zrimi J, Ng Ling A, Giri-Rachman Arifin E, Feverati G, Lesieur C. Cholera toxin B subunits assemble into pentamers - proposition of a fly-casting mechanism. PLoS One. 2010;5(12):e15347. PubMed PMID: 21203571.
[3]. Lesieur C, Cliff MJ, Carter R, James RF, Clarke AR, Hirst TR. A kinetic model of intermediate formation during assembly of cholera toxin B-subunit pentamers. J Biol Chem. 2002 May 10;277(19):16697-704. PubMed PMID: 11877421.
[4]. Feverati G, Achoch M, Vuillon L, Lesieur C. Intermolecular β-Strand Networks Avoid Hub Residues and Favor Low Interconnectedness: A Potential Protection Mechanism against Chain Dissociation upon Mutation. PloS one. 2014;9(4):e94745.
[5]. [4]. Lesieur C. The Assembly of Protein Oligomers: Old Stories and New Perspectives with Graph Theory. ISBN 980-953-307-1130-3. Book title: Oligomerization of Chemical and Biological Compounds, edited by Claire Lesieur, publised by INTECH; in press.

12:35 LUNCH

Working session/discussion

jeu. 12 juin

Sylvie RICARD BLUM

KE-QIN ZHANG

David WALES / Exploring and Analysing Energy Landscapes for Proteins

David J. Wales, Cambridge University, Department of Chemistry
www-wales.ch.cam.ac.uk

Coarse-graining the potential energy surface into the basins of attraction of local minima provides a computational framework for investigating structure, dynamics and thermodynamics in molecular science. Steps between local minima form the basis for global optimisation via basin-hopping and for calculating thermodynamic properties using the superposition approach and basin-sampling. To treat global dynamics we must include transition states of the potential energy surface, which link local minima via steepest-descent paths. We may then apply the discrete path sampling method, which provides access to rate constants for rare events. In large systems the paths between minima with unrelated structures may involve hundreds of stationary points of the potential energy surface. New algorithms have been developed for both geometry optimisation and finding connections between distant local minima, which allow us to treat such systems. A graph transformation approach enables rate constants and committor probabilities to be extracted from kinetic transition networks containing over a million states. Applications will be presented for a range of different protein examples, ranging from atomistic to coarse-grained models.

Selected Publications:

D.J. Wales, Curr. Op. Struct. Biol., 20, 3-10 (2010)
D.J. Wales, J. Chem. Phys., 130, 204111 (2009)
B. Strodel and D.J. Wales, Chem. Phys. Lett., 466, 105-115 (2008)
D.J. Wales and T.V. Bogdan, J. Phys. Chem. B, 110, 20765-20776 (2006)
D.J. Wales, Int. Rev. Phys. Chem., 25, 237-282 (2006)
D.J. Wales, "Energy Landscapes", Cambridge University Press, Cambridge, 2003

12:45 LUNCH

Working session/discussion