VI INTERNATIONAL CONFERENCE · PDF fileWelcome to VI International Conference BIFI2014, ... The relevance of combining computations with experiments for these systems will be ... SPM

VI INTERNATIONAL CONFERENCE BIFI2014

1

Contents

Organizing committee .............................................................................................................................................. 2

Conference Secretariat .............................................................................................................................................. 2

Invited speakers ........................................................................................................................................................ 3

Foreword .................................................................................................................................................................. 4

Program .................................................................................................................................................................... 5

Abstracts ................................................................................................................................................................... 8

List of participants .................................................................................................................................................. 70


2

Organizing committee

Javier Borge-Holthoefer (BIFI Institute)

Pierpaolo Bruscolini (BIFI Institute and Department of Theoretical Physics, U. Zaragoza)

Alberto Castro (ARAID Foundation, BIFI Institute)

Bruno Contreras-Moreira (ARAID Foundation, Estación Experimental de Aula Dei-CSIC)

María Fillat (Department of Biochemistry and Molecular and Cell Biology, U. Zaragoza)

Sergio Perez-Gaviro (ARAID Foundation, BIFI Institute)

Conference Secretariat

Beatriz Antolí

Isabel Vidal


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Invited speakers

Molecular Modeling (January 22nd). Co-organized by ZCAM

Emilio Artacho (Nanogune, Donostia-San Sebastián, Spain, and Basque Foundation for Science,

Ikerbasque)

Javier Brey Abalo (Universidad Sevilla, Sevilla, Spain)

Paolo Carloni (German Research School for Simulation Sciences, Jülich, Germany)

Alberto García (Institut de Ciència de Materials, CSIC, Barcelona. Spain)

Michel Mareschal (Zaragoza Center for Advanced Modeling, University of Zaragoza)

Modesto Orozco (Institut for Reserch in Biomedicine, Barcelona Supercomputing Center and

University of Barcelona, Barcelona, Spain)

Ignacio Pagonabarraga (Fisica Fonamental, Universitat de Barcelona)

Rubén Pérez (Universidad Autónoma de Madrid, Madrid, Spain)

Stephan Roche (Institut Català de Nanociència i Nanotecnologia-ICREA, Barcelona, Spain)

Ángel Rubio (Universidad del País Vasco, Donostia-San Sebastian, Spain)

María José Ruiz Montero (Universidad de Sevilla, Sevilla, Spain)

Biological Systems (January 23rd)

Joaquin Dopazo (Centro de Investigación Príncipe Felipe, Valencia, Spain)

Wolfang Hess (Institute of Biology III, University Freiburg)

Rémi Monasson (Laboratoire de Physique Théorique de l'ENS, CNRS & UPMC, Paris, France)

Computational Physics (January 24th)

Sergio Gómez (Dept. Enginyeria Informàtica i Matemàtiques Universitat Rovira i Virgili, Tarragona,

Spain)

Wolfhard Janke (Institut für Theoretische Physik Universität Leipzig, Leipzig, Germany)

Itamar Procaccia (Department of Chemical Physics, Weizmann Institute of Science, Rehovot, Israel)


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Foreword

Every two years since 2004, the BIFI Institute holds an International Conference. The aim of these

conferences is to bring together researchers and experts from different institutions to discuss the recent

advances on any specific area, as well as to promote collaborations between all participants or reinforce

them, in an international and pleasant environment.

As we all know, Computation is manifestly present in our daily lives. From the pioneering mechanical

programmable computer prototype Z1, by Konrad Zuse,in the late 30's and the first electronic general-

purpose re-programmable computer ENIAC, by John Presper Eckert and John William Mauchly, in the

early 40's, Computation has been a paradigm of continuous development to our days. In fact,

Computation has revealed as an essential tool in many areas of Science, as in Biology, Medicine,

Biochemistry or Physics, making possible relevant advances and further investigations in many fields

that would not be affordable by any other manner.

This year our International Conference is rooted on the above observations and aims to bring together

scientists from whatever discipline where Computation is required as an essential tool for their

research. Under the title "Exploring the role of computation in Science: from Biology to Physics", we

intend to cover different fields related with Molecular Modeling, Biological Systems or Computational

Physics. Several computational techniques as Monte Carlo simulations, Molecular Dynamics, Quantum

Chemistry, optimization techniques, as well as new high-performance computing paradigms, applied to

different areas, will be discussed.

We expect this conference to be an occasion for outstanding scientists and industry researchers to meet

and discuss their recent developments, original ideas and future challenges in this fast moving field.

Welcome to VI International Conference BIFI2014,

Sergio Pérez Gaviro


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Program

Wednesday, January 22nd (Co-organized by the ZCAM)

08:30 – 09:00/ Registration 09:00 – 09:15/ Welcome ceremony Session I – Chair: Alberto Castro 09:15 – 10:00/ Paolo Carloni. Predicting structural ensembles of intrinsically disordered proteins by multi-scale modeling. 10:00 – 10:30/ Modesto Orozco. The multiscale nature of DNA 10:30 – 11:00/ Rubén Pérez. Understanding the image contrast in Tunneling and Force Microscopies: From graphene to biomolecules. 11:00 – 11:15/ Guilherme Vilhena. Antibody adsorption over graphene: an atomistic MD and MF-AFM study 11:15 – 11:45/ Coffee Break 11:45 – 12:15/ María José Ruiz Montero. DSMC Study of Granular Fluids 12:15 – 12:45/ Javier Brey Abalo. Adiabatic piston in non-equilibrium situations: granular and molecular gases 12:45 – 13:15/ Michel Mareschal. Shocks in Fluids: Is there a Theory? 13:15 – 13:45/ Ignacio Pagonabarraga. Modeling emergent patterns in active matter: From molecular motors to microswimmer suspensions 13:45 – 15:30/ Lunch Break Session II – Chair: Michel Mareschal 15:30 – 16:00/ Stephan Roche. Order N Computational Methods for Exploring Charge, Phonon and Spin Transport in Condensed Matter: Benchmarking Materials and Assessing Novel Applications 16:00 – 16:30/ Emilio Artacho. Using TDDFT to calculate the electronic stopping power for ions shooting through solids from first principles 16:30 – 16:45/ Juan José Galano Frutos. Molecular Dynamic Simulations of Anion/Protein Unbinding Interactions in two similar Apoflavodoxin structures. Insights about the complex FMN-flavodoxin binding scenario. 16:45 – 17:15/ Coffee Break 17:15 – 17:45/ Alberto García. Large-scale ab-initio calculations with SIESTA-PEXSI 17:45 – 18:15/ Angel Rubio. Light-induced processes in finite and extended systems from TDDFT 18:15 – 18:30/ Javier Romero-García. Biocomputational Study of a Mycoplasma Glycolipid Synthase. Structural Data Integration and Molecular Simulations Guide Experimental Approaches.


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Thursday, January 23rd

Session I – Chair: Bruno Contreras Moreira 09:00 – 09:50/ Joaquín Dopazo. The revolution of genome sequencing opens the door to precision medicine 09:50 – 10:40/ Wolfgang R. Hess. Double-comparative transcriptomics shows adaptive flexibility of bacterial transcriptomes 10:40 – 11:10/ Sara López-Gomollón. ILLUMINAting the role of miRNAs during fruit development 11:10 – 11:40/ Coffee Break Session II – Chair: Pierpaolo Bruscolini 11:40 – 12:30/ Rémi Monasson Inferred Model of the Prefrontal Cortex Activity Unveils Task-Related Cell Assemblies and Memory Replay 12:30 – 13:00/ Leonardo D. Garma. A new Similarity Index for comparing non-sequential protein segments 13:00 – 13:30/ Juan Carro . An in silico search for glucose-methanol-choline oxidoreductases with interesting features in ten Polyporales genomes 13:30 – 15:30/ Lunch Break Session III – Chair: María F. Fillat 15:30 – 16:00/ Laura Botello-Morte. Identification of new interacting partners of the global regulator FurA from Anabaena sp. PCC 7120 16:00 – 16:30/ Esther Broset. A point mutation in the sensor domain of the PhoR kinase severely impacts on Mycobacterium tuberculosis pathogenicity 16:30 – 16:50/ Coffee Break 16:50 – 17:20/ Bruno Contreras-Moreira. Phylogenetic analysis of resequenced organelle genomes: the case of the Brachypodium distachyon complex chloroplasts 17:20 – 17:50/ María Sebastián-Valverde. Structural basis for the interaction of the FAD synthetase from the human pathogen Streptococcus pneumoniae with its ligands 18:00 – 19:00/ Poster Session 19:00/ General Assembly (BIFI members only) 21:30/ Social Dinner


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Friday, January 24th

Session I – Chair: Sergio Perez-Gaviro 09:00 – 09:50/ Wolfhard Janke. Monte Carlo Simulations of Polymer Adsorption and Aggregation in Generalized Ensembles 09:50 – 10:40/ Itamar Procaccia. Statistical Physics of Pure Barkhausen Noise 11:40 – 12:10/ Coffee Break 12:10 – 12:30/ Chihiro H. Nakajima. Statistical Mechanics Model for Integer Factorization 12:30 – 12:50/ Marco Baity-Jesi. Phase Transition in 3d Heisenberg Spin Glasses with Strong Random Anisotropies, through a Multi-GPU Parallelization 12:50 – 13:15/ Roberto Preatoni. A global approach to design high speed complex digital systems 13:15 – 15:30/ Lunch Break Session II – Chair: Yamir Moreno 15:30 – 16:20/ Sergio Gómez. Interplay between awareness and epidemic spreading in networks 16:20 – 16:40/ Jordi Duch. Quantum Navigation and Ranking in Complex Networks 16:40 – 17:00/ Mauro Faccin. Community Detection in Quantum Systems 17:00 – 17:20/ Joaquin Sanz. Dynamics of interacting epidemics 17:20 – 17:40/ Coffee Break Session III – Chair: Joaquin Sanz 17:40 – 18:00/ Sergio Arregui. Impact evaluation of novel anti tuberculosis vaccines. 18:00 – 18:20/ Carlos Borau. Brownian Dynamics Simulation of Cytoskeletal Networks: the Mechanosensing Process 18:20 – 18:40/ Emanuele Cozzo. Contact-based social contagion in multiplex networks 18:40 – 19:00/ Sandro Meloni. Heterogeneous resource allocation can change social hierarchy in public goods games. 19:00 – 19:20/ Carlos Gracia-Lázaro. Irreversibility in the transition to cooperation in complex networks 19:20/ Closing Remarks


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Abstracts

Talks. Wednesday 22nd VI INTERNATIONAL CONFERENCE BIFI2014

9

Predicting structural ensembles of intrinsically disordered proteins by multi-scale modeling

Paolo Carloni1

1 German Research School for Simulation Sciences GmbH, Forschungszentrum Jülich GmbH, RWTH Aachen University

Intrinsic Disordered proteins (IDPs) constitute as much as one third of the human genome. Several of those are associated with a variety of diseases, including cancer and neurodegenerative diseases. Unfortunately, rational drug design targeting IDPs poses serious challenges since these proteins exist as dynamic, highly flexible structural ensembles, continuously undergoing conformational conversions. We are using a variety of molecular simulation approaches, from all atom MD to coarse-grain MC and to hybrid QM/MM, in an effort at characterizing IDPs ensembles, and in particular at predicting the intriguing effects on IDPs conformations caused by disease-linked mutations and ligand binding. I will focus in this talk on proteins involved in prion and Parkinson's diseases. The relevance of combining computations with experiments for these systems will be emphasized.


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The Multiscale Nature of DNA

Modesto Orozco1

1Molecular Modeling and Bioinformatics Unit, IRB Barcelona – University of Barcelona

DNA is not only the major carrier of genetic information, but also a molecule with fascinating biotechnological possibilities, linked to its unique structure and physical properties. Modeling of DNA is a major challenge, because of its large flexibiliy, extreme charge density and specially because of its multi-scale nature that goes from subnanometer to the millimeter scale and from femtosecond to minutes. During my talk I will review methodological approaches developed to solve the multiscale problem and to model DNA from the nucleobase to the entire chromatin level.


11

Understanding the image contrast in Tunneling and Force Microscopies: From graphene to biomolecules

Rubén Pérez

SPM Theory and Nanomechanics Group, Departamento de Física Teórica de la Materia Condensada and Condensed Matter Physics Center (IFIMAC), Universidad Autónoma de Madrid, E-28049 Madrid, Spain

We’ll review the computational tools and protocols developed in our group in order to study the mechanical and transport properties of materials, and its application to the understanding of the atomic-resolution images obtained with the scanning tunneling (STM) and the force microscope (AFM) by different experimental groups.

Firstly, we’ll focus on tuning of the electronic properties of graphene through the creation of defect [1] and edge states, looking, in particular, to the connection of graphene with metal surfaces. Combining high resolution STM experiments and DFT calculations, we have unambiguously unveiled the atomic structure of the boundary between a graphene zigzag edge and a Pt(111) step [2]. The graphene edges minimize their strain by inducing a 3-fold edge-reconstruction on the metal side, preserving an unoccupied electronic state, exclusively localized in the C-edge atoms of a particular graphene sublattice, which could be used to develop new dual-channel devices.

Metal oxides play a key role in a wide range of technological applications. While in many cases the same FM-AFM image can be explained by different models, and even different underlying tip-sample interactions, we show here that the combination of force spectroscopy (FS) measurements and first-principles simulations can provide an unambiguous identification of the tip structure and the image contrast mechanism in rutile TiO2 (110) [3] and anatase TiO2 (101) surfaces. In the case of STM, we have made a comprehensive study of the (2√2x√2)R45º missing row reconstruction of the Cu(100) surface, using different tips and systematically varying bias voltage and tip sample distance, to explore the rich variety of image contrasts observed in the experiments [4,5]. Our results achieve a conclusive understanding of fundamental STM imaging mechanisms and provide guidelines for experimentalists to achieve chemically selective imaging by choosing appropriate imaging parameters.

Finally, we’ll present our recent work on the structure and functionality of biological systems in their native liquid environment. We’ll discuss the application of large-scale steered Molecular Dynamics simulations, based on classical potentials developed by the molecular biology community and the use of GPUs as processing units, provide insight into the protein-graphene biocompatibility, the flexibility map of human antibodies, and the hydration properties of self-assembled monolayers of single-stranded DNA and its possible use as a label-free DNA sensor.

1] M. M. Ugeda et al., Phys. Rev. Lett. 107,116803 (2011)

[2] P. Merino et al., submitted to Nanoletters (2013)

[3] A. Yurtsever et al., Phys. Rev. B 85, 125416 (2012).

[4] M. Z. Baykara et al., Phys. Rev. B 87 ,155414 (2013). (Editors’ Suggestion)

[5] H. Monig et al., ACS nano DOI:10.1021/nn4045358 (2013)


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Antibody adsorption over graphene : an atomistic MD and MF-AFM study

J.G. Vilhena1, 2, A. C. Dumitru1, Elena T. Herruzo1, Jesus I. Mendieta-Moreno2, Pedro A. Serena1, Ricardo García1, Rubén Pérez2, 3

Proteins interaction with surfaces has great technological relevance for the development of biocatalysts, implants and biosensors. Recent advances on both molecular-dynamics (MD) simulations and atomic-force-microscopy (AFM), allow studying such large systems with atomistic detail. Here we have combined MD simulations with high-resolution multi-frequency-AFM experiments to study the adsorption of the IgG antibody (150kDa) over graphene. IgG provides the majority of antibody-based immune response. Therefore studying its biocompatibility/activity over graphene is of interest to address the graphene usage as an implant material as well as to develop more sensitive immunoassays.

We have developed a protocol combining steered-MD simulations and long (>150ns) equilibration runs to address several key open questions concerning protein adsorption: the interaction mechanisms behind the adsorption, the role of the water molecules in such process, and under which conditions the protein unfolds due to the interaction with the substrate. Moreover we determine the most favorable adsorption orientation of the IgG, which in turn allows us to set up a strategy to control the IgG adsorption over graphene. Both the bioactivity and adsorption orientation statistics are in good agreement with experiments.

[1] Antibody adsorption over graphene; submitted to NanoLetters

1 Instituto de Ciencia de Materiales de Madrid, CSIC, Madrid, Spain

2 Departamento de Física Teórica de la Materia Condensada, Universidad Autónoma de Madrid E-28049

Madrid, Spain

3 Condensed Matter Physics Center (IFIMAC), Universidad Autónoma de Madrid, E-28049 Madrid, Spain


13

DSMC Study of Granular Fluids

María J. Ruiz Montero, J. Javier Brey.

Física Teórica. Facultad de Física. Universidad de Sevilla (Spain)

The Direct Simulation Monte Carlo method (DSMC) was introduced by G. Bird [1] to mimic the dynamics of the particles of a dilute gas. It is more efficient than Molecular Dynamics to study dilute systems, and has the additional advantage of allowing to exploit the possible symmetries of the state under consideration. DSMC has been used with great success to investigate the properties of dilute granular systems in rather different states. For instance, it has been used to study the distribution function of a granular gas in the homogeneous cooling state, the behavior of the energy fluctuations close to the clustering instability, the value of a new transport coefficient coupling the heat flux and the density gradient, the lack of energy partition in binary mixtures, etc. In this talk, the general ideas of DSMC will be discussed, and some results for granular fluids obtained using this method will be presented.

[1] G.A. Bird, Molecular Gas Dynamics and the Direct Simulations of Gas Flows (Clarendon Press, Oxford, 1994).


14

Adiabatic piston in non-equilibrium situations: granular and molecular gases

J. Javier Brey.

Física Teórica. University of Sevilla (Spain)

The steady state reached by two gases separated by an adiabatic piston will be investigated in two rather different cases. First, two vibrated granular gases will be considered. It will be shown that the system exhibits a non-equilibrium phase transition, with spontaneous symmetry breaking. Afterwards, a molecular gas with a temperature gradient generated by the walls will be discussed.


15

Shocks in Fluids: Is there a Theory?

Michel Mareschal1

1 Zaragoza Center for Advance Modeling, University of Zaragoza.

Shock fronts in dense fluids are a few molecular diameters thick and sustain large thermodynamic forces, leading to deviations from the traditional non-equilibrium phenomenology. We compare direct MD modeling with possible generalizations of Navier-Stokes and Fourier laws. The most accurate description found goes back to Maxwell.


16

Modeling emergent patterns in active matter: From molecular motors to microswimmer suspensions

Ignacio Pagonabarraga Mora1

1 University of Barcelona

Active systems generate motion due to energy consumption, usually associated to their internal metabolism or to appropriate, localized, interfacial chemical reactivity. As a result, these systems are intrinsically out of equilibrium and their collective properties emerge as a balance between their direct interactions and the indirect coupling to the medium in which they displace. Therefore, a dynamical approach is required to analyze their evolution and quantify their selfassembly and ability to generate intermediate and large scale stable structures.

The modelling of such systems is challenging because of the different length scales involved. I will describe different mesocopic approaches that capture essential features of model active systems, the capabilities and limitations


17

Order N Computational Methods for Exploring Charge, Phonon and Spin Transport in Condensed Matter: Benchmarking Materials and Assessing Novel

Applications

Stephan Roche

ICREA Research Professor, Catalan Institute of Nanoscience and Nanotechnology-ICN2

I will present a successful computational strategy to investigate quantum (charge, phonon and spin) transport in structurally or/and chemically complex materials such as graphene, topological insulators, or organic matter, for which it is necessary to go beyond phenomenological approaches. The possibility to combine first principles calculations with tight-binding models, together with the development of order N algorithms which are free from any matrix inversion/diagonalization give access to the study of quantum transport phenomena in realistic models of complex materials containing up to 1 Billion atoms. Such methodologies allow direct comparison with experiments, and can hence serve as guiding tools for technology optimization, as well as new tools for discovering quantum phenomena out of reach from conventional perturbative treatments and semi-classical transport approaches.

One illustration will be the quantitative analysis on the transport properties of the damage produced during the wafer-scale production of graphene through chemical growth (CVD), or the mechanical/chemical exfoliation and chemical transfer to versatile substrates, followed by the device fabrication. Fundamental properties of charge transport in polycrystalline graphene, accounting the variability in average grain sizes and grain boundaries imperfections as observed in real samples grown by CVD will be presented, together with their relevance for device optimization and diversification of technological functionalities. Other illustrations will include thermal transport in hybrid boron nitride (BN)/graphene materials, or BN/graphene heterostructures which display fascinating physics such as the Hofstadter butterfly.

A second type of applications will focused on the study spin-orbit interaction induced by dilute ad-atom (gold, thallium) deposits on graphene. Unique phenomenon of the spin-dynamics in graphene (such as Spin Quantum Hall effect), as well as quantitative evaluation of spin precession times and spin-relaxation times as a function of charge density will be reported. Such findings will be shown to open novel perspectives for spin manipulation, contributing to the future advent of non-charge based revolutionary information processing and computing.

[1] L. E. F. Foa Torres, S. Roche, and J. C. Charlier, Introduction to Graphene-Based Nanomaterials: From Electronic Structure to Quantum Transport (Cambridge University Press, Cambridge, 2014).

[2] S. Roche, N. Leconte, F. Ortmann, A. Lherbier, D. Soriano, and J.-C. Charlier, Solid State Communications 152, 1404 (2012).

[3] D. Van Tuan, J. Kotakoski, T. Louvet, F. Ortmann, J. C. Meyer, and S. Roche, Nano Lett. 13, 1730−1735 (2013)

[4] A. Cresti, D. Van Tuan, D. Soriano, S. Roche, Phys. Rev. Lett. (submitted)

[5] R. Martinez-Gordillo, S. Roche, F. Ortmann, M. Pruneda, Phys. Rev. Lett.


18

Using TDDFT to calculate the electronic stopping power for ions shooting through solids from first principles

Emilio Artacho1

1 Nanogune and DIPC, Tolosa Hiribidea 76, 20018 San Sebastián, Spain. Theory of Condensed Matter, Cavendish Laboratory, University of Cambridge

Ions shooting through materials give rise to both electronic and nuclear processes that affect their structural integrity and functionality. This kind of radiation damage is important for the the nuclear, aviation and space industries, as well as for human health, in terms of particle radiotherapy. In such processes, electronic excitations, as measured by the electronic stopping power, are important in the fundamentals and in their effect. Electronic stopping is quite well understood in specific limiting situations, most prominently for simple metals, based on the theory for the homogeneous electron liquid. The understanding for other kinds of materials, especially in the low velocity regime is still very poor, with every new experiment bringing about unexpected new qualitative features. in recent years we have developed a technique for the first-principles simulation of electronic stopping power in real materials, which has been quite successfully applied to wide band-gap insulators, noble metals and semiconductors. In this talk I will briefly review the technique and its key results so far.


19

Molecular Dynamic Simulations of Anion/Protein Unbinding Interactions in two Similar Apoflavodoxin structures. Insights about the complex FMN-flavodoxin binding scenario.

Juan José Galano Frutos1,2, Javier Sancho Sanz1,2

1 Department of Biochemistry and Molecular and Cell Biology, University of Zaragoza, 50009, Zaragoza, Spain.

2 Institute for Biocomputation and Physics of Complex Systems (BIFI), 50018, Zaragoza, Spain.

The Hp-fld is an essential protein that is being used as a target to develop new antimicrobials [1]. The binding of FMN cofactor to Helicobacter pylori's flavodoxin (Hp-fld) is a very complex scenario. Some studies have been carried out about this issue, and several possible association mechanisms proposed [2-4]. Nevertheless, many aspects of that mechanisms are yet to be fully clarified as for example the roles of different anions often bound to FMN phosphate binding subsite [5,6]. In this work, we investigated from a computational point of view the anion/protein interactions of one chloride and one sulphate bound to the FMN binding pockets of the homologous apoflavodoxin structures 2BMV [5] and 1FTG [6] respectively. Molecular dynamics simulations performed for both anions (50 and 10 runs respectively). Meticulous anion/protein conformation, solvation, interaction forces and statistical analyses were carried out. The temperature factor was also evaluated. In the chloride case, on 45 of 50 runs (up to 20 ns) the anion spontaneously left its original binding site, doing so in a relatively short time and through no preferred exit route. In the other five chloride runs and for the sulphate case (up to 100 ns) the anions remained tightly bound; one very characteristic binding conformation was observed for such cases. A ‘step-by-step’ desolvation mechanism in the outgoing anion cases was observed. So, this study allows us to add new clues to the complex FMN/protein binding mechanism, and in general it could provide insights into the discovery of new small ligand as possible drugs against Hp.

[1] Cremades N., Bueno M., Toja M. and Sancho J. (2005) Biophys. Chem. 115, 267−276.

[2] Ayuso-Tejedor S., Abian O.,Velazquez-Campoy A. and Sancho J. (2011) Biochemistry 50, 8703-8711.

[3] Pueyo J. J., Curley G. P. and Mayhew, S. G. (1996) Biochem. J. 313 (Pt 3), 855−861.

[4] (19) Lostao A., Daoudi F., Irun M. P., Ramon A., Fernande-Cabrera C., Romero A., and Sancho J. (2003) J. Biol. Chem. 278, 24053−24061.

[5] Martinez-Julvez M., Cremades N., Bueno M., Perez-Dorado I., Maya C., Cuesta-Lopez S., Prada D., Falo F., Hermoso J. A., and Sancho, J. (2011) Proteins, 2011, 69, 581−594.

[6] Genzor C. G., Perales-Alcon A., Sancho J. and Romero A. (1996) Nat. Struct. Biol. 3, 329−332.


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Large-scale ab-initio calculations with SIESTA-PEXSI

Lin Lin1, Georg Huhs2, Alberto García3, Chao Yang1

1 Lawrence Berkeley National Laboratory, USA.

2 Barcelona Supercomputing Center.

3 Institut de Ciència de Materials de Barcelona (ICMAB-CSIC).

The possibility of treating large systems with first-principles electronic-structure methods has opened up new research avenues in many disciplines. In particular, the SIESTA program [1] has become quite popular and is increasingly being used by researchers in geosciences, biology, and engineering (apart from those in its natural habitat of materials physics and chemistry). SIESTA's efficiency stems from the use of strictly localized basis sets and from the implementation of linear-scaling algorithms which can be applied to suitable systems. A very important feature of the code is that its accuracy and cost can be tuned in a wide range, from quick exploratory calculations to highly accurate simulations matching the quality of other approaches, such as plane-wave methods.

We have implemented in the SIESTA code a new electronic-structure solver based on the Pole Expansion and Selected Inversion (PEXSI) technique [2]. This approach scales at most quadratically with system size by exploiting in a general way the sparsity of the Hamiltonian and other matrices involved. It can be applied to all kinds of systems, including metals, and its accuracy is comparable to that of cubic-scaling full diagonalization. PEXSI can use large numbers of processors efficiently due to the near-perfect parallelization over poles and the good scaling of the pole-specific operations, thus enabling the treatment of very large systems in high-performance machines.

[1] Soler J.M., Artacho E., Gale J.D., García A., Junquera J., Ordejón P., and Sánchez-Portal D. (2002) J. Phys.: Condens. Matt. 14, 2745-2779.

[2] Lin L., Chen M., Yang C., and He L. (2013) J. Phys.: Condens. Matter 25, 295501.


21

Light-induced processes in finite and extended systems from TDDFT

Angel Rubio1

1 NanoBio Spectroscopy Group, Departamento de Física de Materiales, Universidad del País Vasco.European Theoretical Spectroscopy Facility (ETSF)

In this talk we will review the recent advances within density-functional and many-body based schemes to describe spectroscopic properties of complex systems with special emphasis to modelling time and spatially resolved electron spectroscopies (including transient pump-probe techniques). Pros and cons of present functionals will be highlighted and provide insight in how to overcome those limitations by merging concepts from many-body perturbation theory and time-dependent density functional theory. We will discuss some of the theoretical approaches developed in the group (and under development) for the characterisation of matter out of equilibrium, the control material processes at the electronic level and tailor material properties, and master energy and information on the nanoscale to propose new devices with capabilities. We will focus on examples linked to the efficient conversion of light into electricity or chemical fuels ("artificial photosynthesis") and the design on new nanostructured based optoelectronic devices based on inorganic nanotubes, among others. The goal of the group activities in the long-run is to provide a detailed, efficient, and at the same time accurate microscopic approach for the ab-initio description and control of the dynamics of decoherence and dissipation in quantum many-body systems.


22

Biocomputational Study of a Mycoplasma Glycolipid Synthase. Structural Data Integration and Molecular Simulations Guide Experimental Approaches.

Javier Romero-García1, Carles Francisco1, Xevi Biarnés1, Antoni Planas1

1Laboratory of Biochemistry, Institut Químic de Sarrià, Universitat Ramon Llull, Barcelona, Spain.

Glycoglycerolipids are structural components of mycoplasma membranes with a fundamental role in membrane properties and stability. Their biosynthesis is mediated by glycosyltransferases (GT) which catalyze the transfer of glycosyl units from a sugar nucleotide donor to diacylglycerol. The essential function of glycolipid synthases in mycoplasma viability, and the absence of glycoglycerolipids in animal host cells make these GT enzymes a target for drug discovery by designing specific inhibitors. However, rational drug design has been hampered by the lack of structural information for any mycoplasma GT. Most of the annotated GTs in pathogenic mycoplasmas belong to family GT2 (CAZY classification [1]). We had previously shown that MG517 in Mycoplasma genitalium is a GT-A family GT2 membrane-associated glycolipid synthase [2]. We present here a series of structural models of MG517 obtained by homology modeling following a multiple-template approach. The models have been validated by mutational analysis and refined by long scale molecular dynamics simulations. Based on the models, key structure-function relationships have been identified: The N-terminal GT domain has a GT-A topology which includes a non-conserved variable region involved in acceptor substrate binding. Glu193 is proposed as the catalytic base in the GT mechanism, and Asp40, Tyr126,Tyr169, Ile170 and Tyr218 define the substrates binding site. Mutation Y169F increases the enzyme activity and significantly alters the processivity (or sequential transferase activity) of the enzyme [3]. The C-terminal region of MG517, with no sequential or structural homology to any other protein, has been partially modeled combining structure prediction servers and computational biophysics analysis. This region is predicted to be mainly composed of alpha helixes where the apical one has a clear amphipathic character. The last helix is thus proposed as part of the MG517 interaction with the membrane. By means of molecular dynamics simulations, the amphipathic behavior of this helix and its association with the membrane has been validated. Overall, this is the first structural model of any GT-A glycoglycerolipid synthase and provides preliminary insights into structure and function relationships in this family of enzymes.

[1] Cantarel B.L., Coutinho P.M., Rancurel C., Bernard T., Lombard V., Henrissat B. (2009) Nucleic Acids Res. 37, D233-238.

[2] Andrés E., Martínez N., Planas A. (2011) J. Biol. Chem. 286, 35367-35379.

[3] Romero-García J., Francisco C., Biarnés X., Planas A. (2013) PLoS ONE. 8, e81990.

Talks. Thursday 23rd VI INTERNATIONAL CONFERENCE BIFI2014

23

The revolution of genome sequencing opens the door to precision medicine

Joaquín Dopazo1 1Computational Genomics Department, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain.

During the last years we have witnessed an astonishing development of the high throughput technologies. This revolution has had an especial impact in the field of sequencing where the new generations of sequencers can produce enormous amounts of data at affordable prices [1]. Nowadays the bottleneck of discovery has moved from the data production phase to the data analysis and interpretation phases. New ways of understanding and addressing complex biological problems beyond the conventional approaches from the molecular biology are arising from the computational biology [2]. Computational biology scientists have now the possibility of formulating and testing hypothesis as well as querying biological systems from a systems biology perspective using genomic data on gene activity (gene expression, methylation, etc.) and/or functionality (mutational spectrum).

The impact of this genomic revolution in the field of medicine has been enormous. Thus, the concept of personalized medicine has evolved to P4 (Personalized, Predictive, Preventive and Participatory) medicine. In particular, Precision medicine needs of better ways of defining diseases by relating conventional clinical–pathological diagnostic criteria with state-of-the-art molecular profiling methodologies. A more precise diagnostic of the disease, based on the description of their molecular mechanisms would allow creating innovative diagnostic, prognostic, and therapeutic strategies precisely tailored to each patient’s requirements [3]. To achieve this, two main problems need to be addressed from a methodological point of view: how genomic features relate among them to give rise to disease phenotypes and how different measurements of different genomic features (i.e. nucleotide variants, gene expression, methylation, etc.) can be integrated to provide more precise descriptors of disease phenotypes. Both aspects have a strong computational component. In the coming years Biocomputing will become an increasingly important component of Medicine.

[1] Kahvejian, A., Quackenbush, J. & Thompson, J. F. Nat Biotechnol 26, 1125-1133 (2008).

[2] Berger, B., Peng, J. & Singh, M. Nat Rev Genet 14, 333-346 (2013).

[3] Mirnezami, R., Nicholson, J. & Darzi, A. N Engl J Med 366, 489-491 (2012).


24

Double-comparative transcriptomics shows adaptive flexibility of bacterial transcriptomes

Wolfgang R. Hess1, Rolf Backofen2, Jens Georg1, Stephan Klähn1, Matthias Kopf1, Ingeborg Scholz1, Björn Voß1, Christian Weingärtner1 , Patrick Wright1,2

1Genetics and Experimental Bioinformatics, Faculty of Biology, University of Freiburg, Schänzlestr. 1, D-79104 Freiburg, Germany 2Bioinformatics Group, Department of Computer Science, University of Freiburg, Georges-Köhler-Allee 106, D-79110 Freiburg, Germany

The comparative analysis of primary transcriptomes from closely related bacteria, challenged by identical environmental perturbations, is a potentially powerful approach. To enable a double-comparative transcriptomics approach (different conditions and two different organisms) focusing on cyanobacteria, we analyzed the transcriptomes of two Synechocystis strains under 10 different conditions using strand-specific cDNA sequencing. We generated genome-wide transcription start site (TSS) maps, derived operon structures, 5’- and 3’-UTRs and identified 24 conserved asRNAs and 55 conserved small RNAs (sRNAs) with very similar regulation. Such sRNAs constitute a large and heterogeneous class of bacterial gene expression regulators. Much like eukaryotic microRNAs, they typically target multiple mRNAs through short seed pairing, thereby acting as global post-transcriptional regulators. However, the experimental identification of possible targets and therefore their confirmation as functional regulators of gene expression has remained laborious. We have been developing a strategy that integrates phylogenetic information to predict sRNA targets at the genomic scale and reconstructs regulatory networks upon functional enrichment and network analysis (CopraRNA [1]). Furthermore, CopraRNA precisely predicts the sRNA domains for target recognition and interaction. The verification of many new targets by CopraRNA, even for extensively investigated sRNAs, demonstrates its advantages and that CopraRNA-based analyses can compete with experimental target prediction approaches. Thus, these data allow the exact inference of previously unknown riboregulators and of regulatory elements for the regulons activated under conditions most important for photosynthetic growth. Remarkably, we identified a class of genes that lack a specific TSS but instead their mRNA originates from the transcription of an sRNA that clearly accumulates as a discrete and abundant transcript while also serving as the 5’ UTR of the adjacent protein-coding gene. Such an sRNA/mRNA structure, that we named ‘actuaton’, might constitute a means of how bacteria remodel their transcriptional network.

[1] Wright P.R., Richter A.S., Papenfort K., Mann M., Vogel J., Hess W.R., Backofen R., Georg J. (2013) PNAS Plus 110 (37), E3487-E3496.


25

ILLUMINAting the role of miRNAs during fruit development

Sara Lopez-Gomollon1,3,4, Irina Mohorianu2, Gyorgy Szittya1, Vincent Moulton2, Tamas Dalmay1.

1 School of Biological Sciences, University of East Anglia. Norwich NR4 7TJ, UK.

2 School of Computing Sciences, University of East Anglia. Norwich NR4 7TJ, UK.

3 Instituto de Biocomputación y Fisica de Sistemas Complejos. Zaragoza. 50018, Spain

4 Current affiliation: Estación Experimental Aula Dei. EEAD-CSIC. Zaragoza, 50015. Spain.

Understanding the molecular mechanisms of specific plant traits such as fleshy fruit development and ripening is key in future breeding programs. Regulatory small RNAs (sRNAs) have been recently discovered and become one of the most intensively studied fields in molecular biology. MicroRNAs (miRNAs) are the best characterised of the different classes of endogenous small RNAs (sRNAs) that regulate the expression of protein coding gene and they play an important role almost all metabolic pathways, such as fruit development. MicroRNAs negatively regulate the accumulation of mRNAs therefore when they are expressed in the same cells their expression profiles show an inverse correlation. There are a few examples in literature of positively correlated miRNA/target pairs, but it is not known how widespread this phenomenon is. Here, we investigated the correlation between the expression profiles of differentially expressed miRNAs and their targets during tomato fruit development using high throughput sequencing, Northern blot and RT-qPCR. We found an equal number of positively and negatively correlated miRNA/target pairs indicating that positive correlation is more frequent than previously thought. We also found that the correlation between microRNA and target expression profiles can vary between mRNAs belonging to the same gene family and even for the same target mRNA at different developmental stages. Since microRNAs always negatively regulate their targets, the high number of positively correlated microRNA/target pairs suggests that mutual exclusion could be as widespread as temporal regulation. The change of correlation during development suggests that the type of regulatory circuit directed by a microRNA can change over time and can be different for individual gene family members.


26

Inferred Model of the Prefrontal Cortex Activity Unveils Task-Related Cell Assemblies and Memory Replay

Ulisse Ferrari1, Gaia Tavoni1,2, Francesco P Battaglia3, Simona Cocco2, Rémi Monasson1

1Laboratoire de Physique Theorique and 2Laboratoire de Physique Statistique, Ecole Normale Superieure, 24 rue Lhomond Paris, 75005, France 3Donders Centre for Neuroscience, Nijmegen, the Netherland

Cell assemblies are thought to be the units of information representation in the brain, yet their detection from experimental data is arduous. Here, we propose to infer the effective network structure from simultaneously recorded neurons in prefrontal cortex using an inverse Ising model and to define cell assemblies as the co-activated neurons in the dynamics of the resulting abstract neural network. The inferred couplings are potentiated after wakeful experience and the resulting assemblies strongly co-activate during wakeful experience and are found to replay during subsequent sleep. Different dynamical regimes as may be observed across wakefulness and sleep can be reproduced by changing a global input parameter, providing access to rare activity fluctuations, crucial for replay. Across sessions, a variety of different network scenarios is observed, providing insight in cell assembly formation and replay.


27

A new Similarity Index for comparing non-sequential protein segments

Garma Leonardo D.1, Juffer Andre H.1

1 Biocenter Oulu and Department of Biochemistry, University of Oulu, Oulu, Finland

The functional elements of proteins such as catalytic sites or ligand binding pockets frequently consist of sparsely distributed amino acids rather than sequential residues. The vast majority of the available structural alignment tools are not meant for the comparison of clusters of isolated residues [1-3] and thus they are unable to perform comparisons restricted to functional elements. In addition, the metrics used to compare sequences make extensive use of evolutionary and annotated data and not only physical-chemical properties of amino acids[4-6]. Although these metrics have proven to be very useful to classify sequences into different folds without using structural data [7], they introduce an unwanted bias when it comes to the comparison of isolated amino acids and thus a new metric is needed. The aim of this study is to develop a new method for the sequence-free quantitative comparison of non-sequential protein segments on the basis of their structural and chemical features only.

[1] Zhang Y., Skolnick J. (2005). TM-align: a protein structure alignment algorithm based on the TM-score. Nucleic Acids Research. 33 (7): 2302-2309

[2] C. Micheletti and H. Orland, MISTRAL: a tool for energy-based multiple structural alignment of proteins, Bioinformatics, vol. 25, p. 2663-2669 (2009)

[3] Holm L, Rosenström P (2010) Dali server: conservation mapping in 3D. Nucl. Acids Res. 38, W545-549

[4] Yampolsky LY, Stoltzfus A. (2005). The exchangeability of amino acids in proteins. Genetics. 2005 Aug;170(4):1459-72.

[5] Atchley WR, Zhao J, Fernandes AD, Drüke T. (2005). Solving the protein sequence metric problem. Proc Natl Acad Sci U S A. 2005 May 3;102(18):6395-400.

[6] Tomii K, Kanehisa M. (1996) Analysis of amino acid indices and mutation matrices for sequence comparison and structure prediction of proteins. Protein Eng. 1996 Jan;9(1):27-36.

[7] Vilim RB, Cunningham RM, Lu B, Kheradpour P, Stevens FJ. (2004) Fold-specific substitution matrices for protein classification. Bioinformatics. 2004 Apr 12;20(6):847-53.


28

An in silico search for glucose-methanol-choline oxidoreductases with interesting features in ten Polyporales genomes

Patricia Ferreira1, Juan Carro2, Ángel T. Martínez2

1 Departamento de Bioquímica y Biología Molecular y Celular and Instituto de Biocomputación y Física de Sistemas Complejos, Universidad de Zaragoza, Zaragoza;

2Centro de Investigaciones Biológicas, CSIC, Madrid

The aim of this work was to find new glucose-methanol-choline (GMC) oxidoreductases with potential biotechnological applications taking advantage of the great deal of fungal genomes currently available. In order to do so, ten fungal species were selected (Bjerkandera adusta, Phlebia brevispora, Ganoderma sp., Fomitopsis pinicola, Phanerochaete chrysosporium, Dichomitus squalens, Ceriporiopsis subvermispora, Trametes versicolor, Rhodonia placenta and Wolfiporia cocos) from the order Polyporales, which possess the ability of degrading wood and, hence, have the degradative machinery encoded in their genomes. We performed an in silico search through protein sequence homology using cloned enzymes (aryl-alcohol oxidases, glucose oxidases, methanol oxidases, pyranose oxidases, cellobiose dehydrogenases and pyranose dehydrogenases) from related fungi. Once the putative enzymes of each class chosen, their sequences manually curated and annotated, we: i) analyzed their evolutionary relationships by constructing gene phylograms based on their predicted protein sequences; and ii) established their duplication/reduction history during fungal evolution by investigating the number of genes of each enzyme type most probably present at every node in the species evolutionary tree (by reconciliation between our constructed gene tree and the species tree available). Moreover, we modeled almost all the GMC sequences out of the 195 found in the ten genomes using the crystallographic structures of related enzymes as templates to gain insight into their structural variation and hypothesize their probable catalytic properties.


29

Identification of new interacting partners of the global regulator FurA from Anabaena sp. PCC 7120

Laura Botello-Morte, M. Teresa Bes, M. Luisa Peleato and María F. Fillat

Department of Biochemistry and Molecular and Cell Biology and Institute for Biocomputation and Physics of Complex Systems (BiFi), University of Zaragoza, 50009 Zaragoza, Spain.

FurA from the cyanobacterium Anabaena sp. PCC 7120 is a global regulator that controls not only the iron homeostasis but it is also involved in the nitrogen metabolism as well as in the oxidative stress response. This DNA-binding protein contains five cysteine residues, four of them arranged into two redox CXXC motifs (C101VKC104 and C141KPC144) whereas the fifth cysteine (C133) is a common feature among the cyanobacterial orthologs [1]. Since the canonical CXXC motif is indeed an essential, common signature of the active site of thiol-oxidoreductase enzymes, we prompted to evaluate the contribution of these motifs to the functionality of FurA. We have recently demonstrated, for the first time for a Fur-family member, that FurA exhibits disulfide reductase activity [2]. With the aim to identify the FurA reducing partner, GST-pull down assays carried out using crude extracts of Anabaena followed by MALDI-MS/MS analyses. These experiments revealed that FurA is able to interact with several potential partners in the cell. The putative N-acetylmuramoyl-L-alanine amidase All1140, the histone-like DNA-binding protein HU, another FurA molecule and the phosphoribulokinase enzyme PRK were proposed as potential FurA partners. In order to confirm all these interactions in vivo, the proteins detected by pull-down were cloned and bacterial two-hybrid (BACTH) assays were performed. As expected, FurA was confirmed to interact with another FurA monomer, with All1140 as well as with HU. However, we could not detect the interaction between FurA and PRK. Notably, FurA binding partners HU and All1140 have been previously localized in the outer membrane fraction of Anabaena, while FurA itself has been annotated as “cell-binding protein” in the Cyanobase and Uniprot databases. To corroborate whether FurA is present in the cell-wall fraction of the cyanobacterium, localization assays were performed using a protoplast suspension and the supernantant containing the outer membrane and the peptidoglycan fractions of Anabaena. Western blotting analysis showed that FurA entirely localizes in the protoplast fraction, in the cytosol of Anabaena. Since we were unable to find a redox partner of FurA by pull-down experiments, the ability of the regulator to interact with other cyanobacterial electron carriers such as reduced thioredoxin, plastocyanin, ferredoxin or ferredoxin-NADP+ reductase was assessed by chemical crosslinking experiments. Interestingly, a potential interaction between Anabaena FurA and ferredoxin was successfully detected and it will be further analyzed in future assays.

[1] Botello-Morte L., González A., Bes M. T., Peleato M. L. and Fillat M. F. (2013) in Genomics of Cyanobacteria-Advances of Botanical Research (Edited by F. Chauvat C. Cassier-Chauvat), vol. 65, pp. 107-156. Elsevier Ltd., Academic Press.

[2] Botello-Morte L., Bes M. T., Heras B., Fernández-Otal Á., Peleato M. L. and Fillat M. F. (2013). Antioxid. Redox Signal. In press. DOI: 10.1089/ars.2013.5376.


30

A point mutation in the sensor domain of the PhoR kinase severely impacts on Mycobacterium tuberculosis pathogenicity

Esther Broset1,2,7,Wladimir Malaga4, Christophe Guilhot4,5,Roland Brosch6,Carlos Martín1,2,3 and Jesús Gonzalo-Asensio1,2

1Grupo de Genética de Micobacterias, Universidad de Zaragoza,Zaragoza, Spain 2CIBER enfermedades respiratorias. Instituto de Salud Carlos III, Madrid, Spain. 3Servicio de Microbiología, Hospital Universitario Miguel Servet, IIS Aragón, Zaragoza, Spain 4Département Mécanismes Moléculaires des Infections Mycobactériennes, Institut de Pharmacologie et Biologie Structural, CNRS, Toulouse, France. 5Université Paul Sabatier, Toulouse, France 6Institut Pasteur, Integrated Mycobacterial Pathogenomics, Paris, France 7Biocomputation and Physics of Complex Systems Institute (BIFI), University of Zaragoza, Zaragoza, Spain. The Mycobacterium tuberculosis PhoP/PhoR two-component signal transduction system regulates well-known virulence pathways including: secretion of the major virulence factor ESAT-6 and production of immunomodulatory lipids. Consequently, mutations in phoP results in attenuation of M. tuberculosis [1; 2] and are indeed the founding principle for the construction of the live attenuated vaccine candidate MTBVAC [3]. However, although the role of PhoP has been extensively documented, the structure-function mechanistics of PhoR remain to be elucidated. In this work, we propose a structure for PhoR based on domain structures of related proteins. Our results suggest that PhoR is a membrane protein able to auto-phosphorylate upon reception of a yet unknown environmental signal and subsequently phosphorylates its cognate transcriptional regulator PhoP. Further, phylogenetic analyses of PhoR in related members of the M. tuberculosis complex indicate a G71I mutation exclusively present in M. bovis and M. africanum. This mutation lies in the putative sensor domain of PhoR and severely impacts on regulation of PhoP-dependent phenotypes. Specifically, we use M.tuberculosis H37Rv carrying the PhoR G71I mutation to demonstrate that mutants are unable to secrete ESAT-6 and to produce acyltrehalose-based lipids. Confirming these observations, we also demonstrate that G71I mutants show decreased mRNA expression of PhoP-regulated genes. Finally, we carry out ex vivo experiments of macrophage replication and virulence in mice to test the relevance of this G71I mutation. Our results demonstrate an impaired multiplication

in macrophages as well as reduced virulence for SCID mice as demonstrated by longer time-to-death in mice infected with strains carrying the mutated phoR allele. Taken together, these results indicate that in addition to PhoP, its cognate sensor kinase PhoR is essential for M. tuberculosis virulence.

[1] Gonzalo-Asensio J, Soto CY, Arbues A, Sancho J, del Carmen Menendez M, Garcia MJ, Gicquel B, Martin C (2008). J Bacteriol 190:7068-7078.

[2] Chesne-Seck ML, Barilone N, Boudou F, Gonzalo Asensio J, Kolattukudy PE, Martin C, Cole ST, Gicquel B, Gopaul DN, Jackson M (2008) a. J Bacteriol 190:1329-1334.

[3] Arbues A, Aguilo JI, Gonzalo-Asensio J, Marinova D, Uranga S, Puentes E, Fernandez C, Parra A, Cardona PJ, Vilaplana C, Ausina V, Williams A, Clark S, Malaga W, Guilhot C, Gicquel B, Martin C (2013). Vaccine 31:4867–4873.


31

Phylogenetic analysis of resequenced organelle genomes:

the case of the Brachypodium distachyon complex chloroplasts

Carlos P. Cantalapiedra1, Diana López-Álvarez2, Sean Gordon3, John P. Vogel,3, Pilar Catalán2, Bruno Contreras-Moreira1,4

1 Dpt of Genetics and Plant Production, Estación Experimental de Aula Dei-CSIC, Zaragoza, Spain

2 Dpt of Agriculture and Environmental Sciences, University of Zaragoza, Huesca, Spain

3 USDA-ARS-WRRC, Albany, CA, USA

4 Fundación ARAID, Zaragoza, Spain

Chloroplast genomes of grasses contain two single copy regions separated by two nearly identical inverted repeats, harboring in total over a hundred genes. These sequences have great value for the reconstruction of the evolutionary history of plants due to their limited size and constrained rate of change. Here we report that high throughput sequencing experiments of grasses of the Brachypodium distachyion complex (B.stacei, B.distachyon and B.hybridum) yield as a by-product sufficient reads to allow the assembly of their plastids. The chloroplasts of a total 54 ecotypes were reconstructed by first filtering chloroplast Illumina pair-end reads based on their k-mer composition, followed by genome assembly, using as reference a collection of sequenced plastids of monocot plant species. Despite the challenge of resolving both inverted repeats, we find that these plastids contain genetic polymorphisms that can help infer their evolutionary history. For instance, a 1Kb insert found in polyploid B.hybridum ABR113, also seen in B.stacei ABR114, contributes to the understanding of its hybrid origin.


32

Structural basis for the interaction of the FAD synthetase from the human pathogen Streptococcus pneumoniae with its ligands

Maria Sebastián-Valverde1,2, Erandi Lira-Navarrete1,2, David Vizarraga1, Ana Serrano1,2, Ramón Hurtado-Guerrero2,3, Marta Martínez-Júlvez1,2, and Milagros Medina1,2

1 Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Ciencias, Universidad de Zaragoza, 50009-Zaragoza, España.

2 Instituto de Biocomputación y Física de Sistemas Complejos (BIFI), Universidad de Zaragoza, 50009-Zaragoza, España.

3 Fundación ARAID, Edificio Pignatelli 36, Zaragoza, Spain.

The pneumococcus Streptococcus pneumoniae is a human pathogen that causes a great number of infections (pneumonia, sinusitis, peritonitis, etc ...) and severe invasive processes (meningitis, septicaemia, etc ...), particularly in the elderly, children and immunosupressed people. Its natural habitat is the human nasopharynx and colonization can occur during the first days of life. As in most prokaryotic organisms, Streptococcus pneumonia has a bifunctional FAD synthetase (FADS) responsible for the in vivo synthesis of the cofactors flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) required to produce all its flavoenzymes and flavoproteins [1]. Despite the SpnFADS crystallographic structure has been reported (PDB 3OP1), no additional information about interaction parameters or efficiency of its Riboflavin Kinase (RFK) and FMN Adenylyl Transferase (FMNAT) activities have been reported. Data obtained in our lab indicate that in spite of the enzyme catalyses both activities, the FMNAT requires strong reducing conditions. That fact contrasts with that described for FAD synthetase from Corynebacterium ammoniagenes, the member of the family so far best characterized [2,3]. Here we show a multidisciplinary analysis of the interaction of SpnFADS with its substrates/products by using both binding equilibrium experimental methods and theoretical docking approaches.

[1] Serrano, A., P. Ferreira, M. Martínez-Júlvez, and M. Medina (2013). The prokaryotic FAD Synthetase family: a potential drug target. Current Pharm Design. 19(14): p. 2637-2648.

[2] Frago, S., A. Velázquez-Campoy, and M. Medina (2009). The puzzle of ligand binding to Corynebacterium ammoniagenes FAD synthetase. J Biol Chem. 284(11): p. 6610-9.

[3] Frago, S., M. Martínez-Júlvez, A. Serrano, and M. Medina (2008). Structural analysis of FAD synthetase from Corynebacterium ammoniagenes. BMC Microbiol 8: p. 160.

Talks. Friday 24th VI INTERNATIONAL CONFERENCE BIFI2014

33

Monte Carlo Simulations of Polymer Adsorption and Aggregation in Generalized Ensembles

Wolfhard Janke1

1 Institut für Theoretische Physik, Universität Leipzig, 04009 Leipzig, Germany, [email protected]

An overview is given on recent results of Monte Carlo simulations of polymer adsorption and aggregation based on a coarse-grained continuum polymer model with bending stiffness and 12-6 Lennard-Jones interactions among the monomers. As adsorbing substrate either a plane surface [1] or the curved inner wall of a spherical cage [2] with varying attraction strength is considered. By means of extensive Monte Carlo simulations in generalized ensembles (multicanonical and parallel tempering methods), rich phase diagrams in the adsorption strength-temperature plane are found, ranging from highly ordered, compact to extended, random coil structures and from desorbed to partially or even completely adsorbed conformations. These findings are identified in canonical and microcanonical [3] analyses with different energetic and structural observables such as the gyration tensor and derived universal quantitites. Some special features of an adsorbing fluctuating membrane [4], allowing for a back-reaction of the polymer and substrate degrees-of-freedom, are also briefly discussed. The talk concludes with very recent results on the aggregation transition of semiflexible polymers in dependence on their bending stiffness [5]. Our data shows that the stiffness plays a key role in whether the system forms amorphous aggregates or twisted bundle structures.

[1] Möddel, M., Bachmann, M., and Janke, W. (2009) J. Phys. Chem. B 113, 3314-3323; Möddel, M., Janke, W., and Bachmann, M. (2010) Phys. Chem. Chem. Phys. 12, 11548-11554; (2011) Comp. Phys. Comm. 182, 1961-1965; (2011) Macromolecules 44, 9013-9019.

[2] Arkin, H. and Janke, W. (2012) Phys. Rev. E 85, 051802-1-9; (2012) J. Phys. Chem. B 116, 10379-10386; (2013) Eur. Phys. J. – Special Topics 216, 181-190; (2013) J. Chem. Phys. 138, 054904-1-8; Marenz, M., Zierenberg, J., Arkin, H., and Janke, W. (2012) Condens. Matter Phys. 15, 43008-1-7.

[3] Janke, W. (1998) Nucl. Phys. B (Proc. Suppl.) 63A-C, 631-633; Junghans, Ch., Bachmann, M., and Janke, W. (2006) Phys. Rev. Lett. 97, 218103-1-4.

[4] Karalus, S., Janke, W., and Bachmann, M. (2011) Phys. Rev. E 84, 031803-1-12.

[5] Zierenberg, J. and Janke, W. (2014) Leipzig preprint.


34

Statistical Physics of Pure Barkhausen Noise

H. George E. Hentschel, Valery Iliyn, Itamar Procaccia1 and Bhaskar Sen Gupta.

1 Dept of Chemical Physics, The Weizmann Institute of Science.

We discuss a model metallic glass in which Barkhausen Noise can be studied in exquisite detail, free of thermal effects and of the rate of ramping of the magnetic field. The mechanism of the jumps in magnetic moment that cause the Barkhausen Noise can be fully understood as consecutive instabilities where an eigenvalue of the Hessian matrix hits zero, leading to a magnetization jump Δm which is simultaneous with a stress and energy changes Δσ and ΔU respectively. Contrary to common belief we find no ``movements of magnetic domain boundaries" across pinning sites, no fractal domains, no self-organized criticality and no exact scaling behaviour. We present a careful numerical analysis of the statistical properties of the phenomenon, and show that with every care taken this analysis is tricky, and easily misleading. Without a guiding theory it is almost impossible to get the right answer for the statistic of Barkhausen Noise. We therefore present an analytic theory, showing that the probability distribution function (pdf) of Barkhausen Noise is not a power law times an exponential cutoff. On the basis of the theory we explain why standard methods to extract the form of the pdf are likely to fail, as indeed happened until now.


35

Statistical Mechanics Model for Integer Factorization

Chihiro H. Nakajima1

1 WPI-AIMR, Tohoku University, Sendai 980-8577, Japan

We proposed a new approach to solve the problem of the prime factorization, by modeling it as the problem of a ground state searching problem of statistical mechanics Hamiltonian [1]. In this model, the system size is given by the logarithm of the target composite integer N to base p, where p is any integer. We performed the replica exchange Monte Carlo simulation [2] of the model in the cases of factoring the product of two large prime numbers and roughly observed that its solving time depends almost exponentially on the system size.

Thus we consider statistical mechanics models for the problems of finding divisors in a composite integer N, focusing on a parameter α = m / n, where m is the number of prime factors included in the N, and n is the system size of the model. The number of the ground states is given by the total number of possible combinations of each prime divisor which grows with m!, when α is large. On the other hand, as α becomes small, such as m=2, the number of the ground states drops drastically. This can be analogous to the behavior of the statistical mechanics model of NP-complete problems [3]. Hence we expect the possibility that a phase transition occurs on a small value α = αc , and the average computational complexity for finding a divisor increases rapidly near αc (there may be a case that the value of αc is 0).

We perform simulations in order to validate the existence of the transition, and the results are discussed in this presentation. Through the behavior of the physical quantities, we attempt to approach the average complexity class of the integer factorization problem.

[1] Nakajima C. H. (2013) Interdisciplinary Information Science, 9, 51-56, also in arXiv:1304.0204.

[2] Hukushima K. And Nemoto K. (1996) J.Phys.Soc.Jpn., 65, 1604-1608.

[3] Monasson R., Zecchina R., Kirkpatrick S., Selman B., and Troyansky L. (1999) Nature, 400, 133-137, Krzakala F., Montanari F., Ricci-Tersenghi F., Semerjian G., Zdeborova L. (2007) Proc. Nat. Acad. Sci., 104, 10318-10323.


36

Phase Transition in 3d Heisenberg Spin Glasses with Strong Random Anisotropies, through a Multi-GPU Parallelization

M. Baity-Jesi¹²³, L.A. Fernández¹², V. Martín-Mayor¹² and J.M. Sanz¹

1 Departamento de Física Teórica I, Universidad Complutense, 28040 Madrid, Spain.

2 Instituto de Biocomputación and Física de Sistemas Complejos (BIFI), 50009 Zaragoza, Spain.

3 Dipartimento di Fisica, Università La Sapienza, 00185 Roma, Italy.

We characterize the phase diagram of anisotropic Heisenberg spin glasses, finding both the spin and the chiral glass transition. We remark the presence of strong finite-size effects on the chiral sector. We find a unique phase transition for the chiral and spin glass sector, in the Universality class of Ising spin glasses. We focus on keeping finite-size effects under control, and we stress that they are important to understand experiments. Thanks to large GPU clusters we have been able to thermalize cubic lattices with up to 64³ spins, over a vast range of temperatures.


37

A global approach to design high speed complex digital systems

Roberto Preatoni1

1 Link Engineering SRL, Casalecchio di Reno (Bologna).

Designing high speed complex digital systems, with respect to the costs and the time to market, requires a multidisciplinary team of experts supported by a methodology and by a state of the art tools. The design of a complex systems dedicated to physics computation, including 256 Virtex 7 FPGA's connected in a 3D torus matrix, has been developed by using a huge set of Mentor Graphics® tools.

High speed digital connections, thermal and mechanical constraints have been managed concurrently starting from the feasibility analysis to the validation tests on a virtual prototype. In our presentation we will describe the methodology used to design PCB's, motherboard and mechanical staff. Finally we will also show few snapshot of the process including Schematic Entry, Layout, Signal & Power Integrity Analysis, Thermal simulations and report of tests run during the validation phase.


38

Interplay between awareness and epidemic spreading in networks

Clara Granell1, Sergio Gómez1, Alex Arenas1

1 Dept. Enginyeria Informàtica i Matemàtiques, Universitat Rovira i Virgili, Tarragona (Spain).

We present the analysis of the interrelation between two processes accounting for the spreading of an epidemics, and the information awareness to prevent its infection, on top of multiplex networks [1]. This scenario is representative of an epidemic process spreading on a network of persistent real contacts, and a cyclic information awareness process diffusing in the network of virtual social contacts between the same individuals. The topology corresponds to a multiplex network where two diffusive processes are interacting affecting each other [2]. In a multiplex network, there are different classes of links, which are assigned to different layers, in this case, the layer of physical contacts where the epidemics spreads, and the layer of virtual contacts where the awareness of the epidemics is propagated. Moreover, every individual belongs to all the layers, thus making this kind of networks different from other structures such as colored graphs or interconnected networks [3]. A tensorial mathematical formalism for multiplex networks can be found in [4].

The analysis of this dynamics using Monte Carlo simulations and a Microscopic Markov Chain Approach (MMCA) [5] reveals the phase diagram of the incidence of the epidemics, and allows capturing the evolution of the epidemic threshold depending on the topological structure of the multiplex and the interrelation with the awareness process. Interestingly, the critical point for the onset of the epidemics has a critical value (meta-critical point) defined by the awareness dynamics and the topology of the virtual network, from which the onset increases and the epidemics incidence decreases.

[1] Granell C., Gómez S., Arenas A. (2013) Phys. Rev. Lett. 111, 128701.

[2] Gómez S., Díaz-Guilera A., Gómez-Gardeñes J., Pérez-Vicente C.J.P., Moreno Y., (2013) Phys. Rev. Lett. 110, 028701.

[3] Mucha P.J., Richardson T., Macon K., Porter M.A., Onnela J.-P. (2010) Science 328, 876-878.

[4] De Domenico M., Solé-Ribalta A., Cozzo E., Kivelä, M., Moreno Y., Porter M.A., Gómez S., Arenas A. (2013) Phys. Rev. X 3, 041022.

[5] Gómez S., Arenas A., Borge-Holthoefer J., Meloni S., Moreno Y. (2010) Europhys. Lett. 89, 38009.


39

Quantum Navigation and Ranking in Complex Networks

Eduardo Sánchez-Burillo1, 2, Jordi Duch3 , Jesús Gómez-Gardeñes2, 4 & David Zueco1, 2, 5

1 Instituto de Ciencia de Materiales de Aragón (ICMA), CSIC-Universidad de Zaragoza, E-50012 Zaragoza, Spain 2 Departamento de Física de Materia Condensada, Universidad de Zaragoza, E-50009 Zaragoza, Spain 3 Departament d'Enginyeria Informàtica i Matemàtiques, Universitat Rovira i Virgili, E- 43007 Tarragona, Spain 4 Instituto de Biocomputación y Física de Sistemas Complejos (BIFI), Universidad de Zaragoza, E-50014 Zaragoza, Spain 5 Fundación ARAID, Paseo María Agustín 36, E-50004 Zaragoza, Spain

Complex networks are formal frameworks capturing the interdependencies between the elements of large systems and databases. This formalism allows to use network navigation methods to rank the importance that each constituent has on the global organization of the system. A key example is Pagerank navigation which is at the core of the most used search engine of the World Wide Web. Inspired in this classical algorithm, we define a quantum navigation method providing a unique ranking of the elements of a network. We analyze the convergence of quantum navigation to the stationary rank of networks and show that quantumness decreases the number of navigation steps before convergence. In addition, we show that quantum navigation allows to solve degeneracies found in classical ranks. By implementing the quantum algorithm in real networks, we confirm these improvements and show that quantum coherence unveils new hierarchical features about the global organization of complex systems.


40

Community Detection in Quantum Systems

Mauro Faccin1,2

1 ISI Foundation, Torino, Italy.

2 Bifi, Zaragoza, Spain.

Determining community structure in interacting systems, ranging from technological to social, from biological to chemical, is a topic of central importance in the study of networks. Extending this concept to apply to quantum systems represents an open challenge and a crucial missing component towards a theory of complex networks based on quantum mechanics. This talk will cover the work primarily in which accomplishes this goal by introducing methods for identifying the community structure of a network governed by quantum dynamics. We found that community structure is relevant for a host of problems commonly faced in quantum physics, and moreover that the state-of-the art methods used to detect communities in complex networks fail to give meaningful results in these cases. We overcome these limitation and present methods to detect communities in quantum systems. To illustrate our approach we turn to a host of examples, including a naturally occurring light-harvesting network, where from first principles we determine a consistent community structure. In certain regimes the communities we determine agree with a partitioning currently done by hand in the quantum chemistry literature. In other regimes, we uncover an improved community structure. Our approach rely on the definition of distances between clusters using two quantum properties: coherent transport and fidelity of the evolved state with the initial one. We define the optimal community structure using a modified modularity function. Merging concepts from quantum physics and complex network theory [1] is providing a bidirectional bridge of relevant analysis tools to address networks in both disciplines. Although this work focuses on extending the concept of community detection to apply to quantum systems, it also opens the door for the application of quantum techniques to determine community structure and other key properties of traditional complex networks. However, our objective here was only to create methods that enable one to determine communities in quantum systems, wherein and as already mentioned, the existing techniques to detect communities in complex networks fail to give meaningful results.

[1] Faccin M., Johnson T., Biamonte J., Kais S., and Migdał P. Degree distribution in quantum walks on complex networks, (2013) Phys. Rev. X, 3:041007.


41

Dynamics of interacting epidemics

Joaquin Sanz1,2, Chen-Yi Xia1,3, Sandro Meloni1, and Yamir Moreno1,2,4

1 Institute for Biocomputation and Physics of Complex Systems, University of Zaragoza.

2 Department of Theoretical Physics, University of Zaragoza.

3 Key Laboratory of Computer Vision and System (Ministry of Education) and Tianjin Key Laboratory of Intelligence Computing and Novel Software Technology, Tianjin University of Technology, Tianjin China. 4 Complex Networks and Systems Lagrange Lab, Institute for Scientific Interchange, Turin, Italy

Contagion phenomena are driven by dynamical principles that can be recognized in many fields of social and medical sciences; from epidemiology to innovation and marketing. Focusing on epidemiological models, the influence of the topological properties of the networks on disease incidence has been exhaustively addressed, as well as the relevance of the main dynamical assumptions underlying each precise model. However, nowadays the need to go beyond the scheme one pathogen-one network is recurrently mentioned as a necessary step towards the understanding spreading of certain interdependent infectious agents. In this work we introduce a new model to describe the dynamics of a couple of diseases whose spreading parameters depend for each disease and individual on her state –infected or susceptible– with respect to the conjugate infection. Our model supposes an initial approach to this problem that is able to offer, simultaneously, either a dynamical description of the non-stationary temporal evolution of an epidemic process and an analytical derivation of epidemic thresholds. Our model adequately foresees the appearance of regions in the parameter space in which, for each disease, the appearance of epidemic outbreaks are conditionally subjected to the prevalence levels of the other disease. Dependences on network sizes and topologies for epidemic thresholds have been exhaustively characterized. Our model predicts atypical behaviors at this particular for diseases interacting according to an absolute crossed immunity scheme, when spreading over highly correlated networks (i.e. two competing strains of the same pathogen). Finite, not vanishing epidemic thresholds appear in this particular scenario, even over scale free networks at the thermodynamic limit. Finally, we show that the model, after a proper fitting of the dynamical parameters, is able to qualitatively reproduce the temporal evolution of a couple of diseases whose interaction is a well known fact: tuberculosis and AIDS, in a region in which the association of these two diseases comes being a major public health problem during the last twenty years: the republic of South Africa.


42

Impact evaluation of novel anti tuberculosis vaccines.

Sergio Arregui1,2, Joaquín Sanz1,2 and Yamir Moreno1,2,3

1 Institute for Biocomputation and Physics of Complex Systems BIFI, University of Zaragoza (Spain)

2 Department of Theoretical Physics, University of Zaragoza (Spain)

3 Complex Networks and Systems Lagrange Lab, Institute for Scientific Interchange, Turin, Italy

Even though tuberculosis is still one of the deadliest infectious diseases over the world, in the last thirty years there have been few pharmacological advances in the topic. More precisely, the main preventive weapon against the disease -the BCG vaccine, only effective against the infectious tuberculosis forms on children- is already 90 years old. For that reason, the development of a new vaccine, aimed at outperforming BCG is a major priority for public health organisms worldwide, and more than 15 independent research teams are nowadays developing new vaccine candidates. The properties of these novel drugs will be revealed within the next decade, once the clinic trials related to the vaccine development process come to an end. Among these candidates, there are vaccines of very different kinds, which make it very likely that the age of the populations on which vaccination is feasible, safe and effective will be different among the diverse new vaccines. For that reason, it is of utmost importance the development of new epidemiological models able to describe, as reliably as possible, the dependence of the disease's dynamics not only on the age of single individuals, but also on the demographic structure of the overall population. In this work, we introduce a new epidemiological model in which a number of factors related to the demographic structure of the population, such as its temporary evolution and the heterogeneity of the contact patterns among individuals of different ages, have been taken into account. Applying our model to evaluate the impact of an eventual vaccination campaign focused on a specific age group, we find out that a vaccination strategy focused on teenagers (15-20 years old) has a greater impact than other strategies focused on any other age group. Our results indicate that the adoption of certain classical oversimplifying hypothesis in what regards the age structure of the population and its mixing patterns introduces systematic biases that nowadays can be and must be eliminated from the models.


43

Brownian Dynamics Simulation of Cytoskeletal Networks:

the Mechanosensing Process

Carlos Borau1,3 ,Taeyoon Kim2, José Manuel García-Aznar1 Roger D.Kamm3

1 Aragón Institute of Engineering Research (I3A) Department of Mechanical Engineering, University of Zaragoza e-mail: [email protected], [email protected] 2 Institute for Biophysical Dynamics, University of Chicago email: [email protected] 3 Departments of Biomechanical Engineering, Massachusetts Institute of Technology email: [email protected]

The actin cytoskeleton network is the dominant structure of eukaryotic cells. It is highly dynamic and plays a central role in a wide range of mechanical and biological functions. Cytoskeleton is composed mainly of actin filaments (F-actin) resulting from the self-assembly of monomeric actin (G-actin) and cross-linked by actin cross-linking proteins (ACPs) whose nature and concentration determine the morphological and rheological properties of the network [1].

These actin filaments are reversibly coupled to membrane proteins and in conjunction with motor proteins from the myosin family, are able to generate contractile force during cell migration. By this mechanism, cells sense the rigidity of their environment and adapt their activity to it [2].

Here, we present a 3-D Brownian dynamics (BD) computational model in which actin monomers polymerize and become cross-linked by ACPs. The dynamic behaviour of molecular motors is also included [3]. In this simulation, actin monomers, filaments, ACPs, and motors experience thermal motion and interact with each other with binding probabilities and defined potentials. Displacements are governed by the Langevin equation, and positions of all elements are updated using the Euler integration scheme.

Mechano-sensing properties of active networks are investigated by evaluating the contraction and the generated stress in response to different extracellular stiffness. Our results reveal, as found in recent literature, that acto-myosin units themselves may act as rigidity sensors [4]. The magnitude and rate of stress generation increased with stress until saturation and followed a Hill force-velocity relationship.

This model has the potential to provide new insight into various biological processes such as cell migration and cytoskeletal remodelling, and can be further refined for investigating actin related phenomena.

[1] Howard J (2001) Mechanics of motor proteins and the cytoskeleton. Sinauer Associates, Sunderland, MA. [2] Mofrad MRK and Kamm RD (2006) Cytoskeletal mechanics: Models and measurements. Cambridge University Press, New York, NY. [3] Kim T, Hwang W, Lee H, and Kamm RD (2009) Computational Analysis of Viscoelastic Properties of Crosslinked Actin Networks. PLoS Comput Biol 5: e1000439. [4] Mitrossilis, D. and Fouchard, J. and Guiroy, A. and Desprat, N. and Rodriguez, N. and Fabry, B. and Asnacios, A. (2010) Single-cell response to stiffness exhibits muscle-like behaviour. PNAS 106(43):18243–18248

Talks. Friday 24th VI INTERNATIONAL CONFERENCE BIFI 2014

44

Contact-based social contagion in multiplex networks

Emanuele Cozzo1,2, Raquel A. Baños1,2, Sandro Meloni1, and Yamir Moreno1,2,3

1Institute for Biocomputation and Physics of Complex Systems (BIFI), University of Zaragoza, Zaragoza 50009,Spain 2Department of Theoretical Physics, University of Zaragoza, Zaragoza 50009, Spain 3Complex Networks and Systems Lagrange Lab, Institute for Scientific Interchange, Turin, Italy

We present a theoretical framework for the study of epidemic-like social contagion in large scale social systems. We consider the most general setting in which different communication platforms or categories form multiplex networks. Specifically, we propose a contact-based information spreading model, and show that the critical point of the multiplex system associated with the active phase is determined by the layer whose contact probability matrix has the largest eigenvalue. Finally, we also show that when the system through which information is disseminating is inherently multiplex, working with the graph that results from the aggregation of the different layers is inaccurate.


45

Heterogeneous resource allocation can change

social hierarchy in public goods games.

Sandro Meloni1 , Cheng-Yi Xia2 and Yamir Moreno1,3

1 Instituto de Biocomputacion y Física de Sistemas Complejos, Universidad de

Zaragoza, E-50018 Zaragoza, Spain. 2 Tianjin Key Laboratory of Computer Vision and System (Ministry of Education) and Key Laboratory of Intelligence Computing and Novel Software Technology, Tianjin University of Technology, Tianjin 300384, P.R.China. 3 Departamento de Física Teorica, Universidad de Zaragoza, E-50009

Zaragoza, Spain.

Nowadays one of the key elements of our societies is the interaction between groups of individuals to achieve a common objective. From a theoretical point of view, the problem has been approached with the tools offered by evolutionary game theory and defined as public goods games (PGG). Here we present a modification of the classical PGG on networks where players are allowed to distribute their investments unevenly, allocating more resources to profitable games and less in unfavorable ones. We show that with this modification an uneven distribution of the wealth naturally emerges reproducing the so-called Pareto principle. In addiction, the analysis of the structure of the most productive environments highlights their organization as the backbone of the network. Our results shed light on the large-scale organization of social and economical systems and give a simple framework for the emergence of features present in real economic scenarios.


46

Irreversibility in the transition to cooperation in complex networks

Carlos Gracia-Lázaro1, Luis M. Floría1,2, Jesús Gómez-Gardeñes1,2, Yamir Moreno1,3

1 Instituto de Biocomputación y Física de Sistemas Complejos (BIFI), University of Zaragoza, Zaragoza 50018, Spain 2 Departamento de Física de la Materia Condensada, University of Zaragoza, Zaragoza 50009, Spain 3 Departamento de Física Teórica, University of Zaragoza, Zaragoza 50009, Spain

In the framework of the evolutionary dynamics of the Prisoner’s Dilemma game on complex networks, we investigate the possibility that the average level of cooperation shows hysteresis under quasi-static variations of a model parameter (the ‘‘temptation to defect’’). Under the ‘‘discrete replicator’’ strategy updating rule, for both Erdös–Rényi and Barabási–Albert graphs we observe cooperation hysteresis cycles provided one reaches tipping point values of the parameter; otherwise, perfect reversibility is obtained. The selective fixation of cooperation at certain nodes and its organization in cooperator clusters, that are surrounded by fluctuating strategists, allows the rationalization of the ‘‘lagging behind’’ behavior observed.

Posters VI INTERNATIONAL CONFERENCE BIFI2014

47

P 01

A mesoscopic description for DNA overstretching induced by melting

Ana Elisa Bergues Pupo1,2, Fernando Falo1,3 and Alessandro Fiasconaro4.

1 Departamento de Física de la Materia Condensada, Universidad de Zaragoza, España.

2 Deparatamento de Física, Universidad de Oriente, Cuba.

3 Instituto de Biocomputación y Física de Sistemas Complejos (BIFI), Zaragoza, España.

4 School of Mathematical Sciences, Queen Mary University of London. Mile End Road, London, UK.

One of the most intriguing and only partially clear phenomena concerning mechanical properties of DNA is the so-called overstretching transition [1,2] which consists in a sudden elongation of the DNA chain of about 70% more than the native length, when a force around 70 pN is applied. Two main mechanisms have been proposed for explaining such a transition: the existence of the unwounded structure termed as S-DNA [2] and a force induced melting where the strands separate via base pair breaking [3]. However, the nature of the transition as well as the molecular structure of the overstretched state remains controversial. Different mesoscopic models have been proposed in order to gain better insights in the understanding of such phenomena [4,5].

In this work, we present a phenomenological dynamical description for the force induced melting mechanism as responsible of the DNA overstretching [6]. This description is supported by two mesoscopic models: the extensible worm like chain model for the stretching and the Peyrard-Bishop-Dauxois (PBD) for the dynamics of the strand separation. The coupling of the stretching and melting dynamics allows us to give a mesoscopic picture of the force induced melting in the DNA overstretching transition. The comparison of the standard PBD model with a modification of the Morse potential which takes into account the interaction with the solvent has been also successfully investigated. We find a good agreement with both the experimental overstretching curve and the asymmetric hysteretic properties with different simulation times.

[1] Smith S. B., Cui Y., and Bustamante. (1996) Science 271, 795.

[2] Cluzel A., Lebrun A. Heller C., Lavery R., and Viovy J.L.(1996) Science 271, 792.

[3] Williams M.C., Wenner J.R., Rouzina I., and Bloomfield V.A., (2001) Biophys. J. 80, 874.

[4] Romano F., Chakraborty D., Doye J., Ouldridge T.E., and Louis A.A., (2013) J. Chem. Phys. 138, 085101.

[5] Fiasconaro A., and Falo F., (2012) Phys. Rev. E 86, 032902. [6] Bergues Pupo A. E., Falo F., and Fiasconaro A., (2013) J. Chem. Phys. 139, 095101.


48

P 02

Aromatic stacking interactions govern catalysis in aryl-alcohol oxidase

Patricia Ferreira1, Aitor Hernández-Ortega2, Fátima Lucas3, Juan Carro2, Victor Guallar3, Ángel T. Martínez2 and Milagros Medina1

1 Instituto de Biocomputación y Física de Sistemas Complejos (BIFI), Universidad de Zaragoza, Mariano Esquillor, Edificio I + D, Zaragoza 50018, Spain.

2CIB, CSIC, Ramiro de Maeztu 9, 28040 Madrid, Spain

3Lifescience, Barcelona Supercomputing Center (BSC), Barcelona, SPAIN

Aryl-alcohol oxidase (AAO) from Pleurotus eryngii is an extracellular flavoprotein that catalyzes the oxidative dehydrogenation of polyunsaturated primary alcohols, using molecular oxygen as final electron acceptor, with the concomitant production of hydrogen peroxide [1]. This oxidase contributes to hydrogen peroxide production as essential substrate for high redox-potential peroxidases during lignin oxidative attack. Lignin removal is a rate-limiting step for carbon recycling in land ecosystems, and also plays a central role in the paper pulp sector and in the production of other chemicals and biofuels in lignocellulose biorefineries, whose sustainability can be increased by the use of biotechnological tools [2]. AAO crystal structure reveals a buried active site with a bottleneck access formed by three aromatic residues, Tyr92, Phe397 and Phe501, limiting solvent connection with the flavin cofactor [3]. Previous migration studies suggested that these residues establish interaction with the alcohol substrate during its access to the AAO active site, where it adopts a final position with the α-carbon near the FAD flavin ring and the side chains of His502 and His546 [4]. From this catalytically position, it seems that Tyr92 might interact through edge-to-plane (T-shaped) stacking interaction, stabilizing the ligand in the active site. In this study, we evaluate the influence of this aromatic-stacking interaction on AAO catalysis. [1]. Hernandez-Ortega, A., Ferreira, P. and Martinez, A. T. (2012). Appl Microbiol Biotechnol. 93, 1395-1410

[2]. Ruiz-Duenas, F. J. and Martinez, A. T. (2009). Microb Biotechnol. 2, 164-177

[3]. Fernández IS, Ruíz-Dueñas FJ, Santillana E, Ferreira P, Martínez MJ, Martínez AT, Romero A. (2009). Acta Crystallogr. D. Biol. Crystallogr. 65, 1196-205

[4]. Hernandez-Ortega, A., Borrelli, K., Ferreira, P., Medina, M., Martinez, A. T. and Guallar, V. (2011). Biochem J. 436, 341-350


49

P 03

pyProCT: Accurate Conformational Cluster Analysis in Python

Víctor Alejandro Gil Sepúlveda1

1 Barcelona Supercomputing Center

As computers and algorithms improve, the size of the ensembles produced in Structural Bioinformatics' computational experiments increase. The analysis of such big datasets becomes more difficult as their size grows, and cluster analysis techniques are being used more and more in order to achieve it.

The result of a cluster analysis, however, can sometimes be of bad quality or totally erroneous. Indeed, clustering algorithm's performance depends greatly on specific traits of the dataset (such as density, cluster size or shape) and the set of parameters used to run it (for instance, the number of clusters parameter in k-means can produce totally artificial partitions).

In order to improve the quality of clustering analysis, we have created pyProCT. pyProCT is a Python-written toolbox that allows users to describe the clustering problem enforcing purpose over how it is done: It finds the clustering algorithm and parameters (including the number of clusters) that best fit user's clustering hypothesis, to then discover new features of the dataset or compress it.

pyProCT code is fully available (open source under MIT license) and is formed of well separated and documented modules that make the code easier to be reused in other projects.


50

P 04

Molecular dynamics simulations of homogeneous states of driven granular mixtures

Nagi Khalil1 and Vicente Garzó1

1 Departamento de Física, Universidad de Extermadura, E-06071 Badajoz, Spain.

Homogeneous states of a granular binary mixture driven by a stochastic bath with friction are considered. The system is fluidized by the presence of an external force or thermostat that tries to mimic the interaction of particles with an effective bath [1,2]. The thermostat is composed by two terms: (i) a drag force proportional to the velocity of particles (Stokes' law) that attempts to model the friction of grains with a viscous interstitial fluid, and (ii) a stochastic force with the form a Gaussian white noise where the particles are randomly kicked between collisions (see Refs. [3,4] where the model is used to describe some experiments). Two different routes have been considered. First, the set of inelastic Enskog-Boltzmann kinetic equations for the granular mixture have been solved by considering the leading terms in a Sonine polynomial expansion. Then, molecular dynamics simulations have been carried out both for time dependent homogeneous states and for homogeneous steady states. Our study has been mainly focused on the two relevant quantities of the problem: the partial temperatures of each species (which are different from the global granular temperature) and the kurtosis or fourth-cumulants (measuring the deviations of the distributions of each species from their Maxwellian forms). Theoretical results are compared against molecular dynamics simulations for different values of the coefficients of restitution and the parameters of the mixture (masses, sizes, concentration and density). The study includes the low-density limit as well as moderately dense binary mixtures.

[1] V. Garzó, M. G. Chamorro, and F. Vega Reyes. Phys. Rev . E 87, 032201 (2013).

[2] N. Khalil and V. Garzó. Phys. Rev . E 88, 052201 (2013).

[3] G. Gradenigo, A. Sarracino, D. Villamaina, and A. Puglisi. EPL 96 14004 (2011).

[4] A. Puglisi, A. Gnoli, G. Gradenigo, A. Sarracino, and D. Villamaina. J. Chem. Phys. 136 014704 (2012).

Posters. VI INTERNATIONAL CONFERENCE BIFI2014

51

P 05

Theoretical models in the study of the catalytic mechanism of the riboflavin kinase activity of a bifunctional FAD synthetase

Isaías Lans1, Marta Martínez-Júlvez2, Beatriz Herguedas3, Pierpaolo Bruscolini4 and Milagros Medina2

1Institut de Neurociències and Unitat de Bioestadística. Facultat de Medicina. Despacho M3-206. Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain.

2Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Ciencias e Instituto de Biocomputación y Física de Sistemas Complejos (BIFI), Universidad de Zaragoza, 50009-Zaragoza, España.

3Neurobiology Division, MRC Laboratory of Molecular Biology, Cambridge, United Kingdom.

4Departamento de Física Teórica, Facultad de Ciencias e Instituto de Biocomputación y Física de Sistemas Complejos (BIFI), Universidad de Zaragoza, 50009-Zaragoza, España.

In most prokaryotic organisms a bifunctional FAD synthetase (FADS) is the responsible of the in vivo synthesis of the cofactors Flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). FADS catalyses two sequential reactions: phosphorylation of Riboflavin (RF) (Riboflavin Kinase (RFK) activity) followed by the adenylylation of synthetized FMN to produce FAD (FMN Adenylyl Transferase (FMNAT) activity). Both cofactors are involved in key processes such us aerobic respiration, photosynthesis, denitrification, sulphur respiration and apoptosis. The FADS crystallographic structure [1] and other two ones of its RFK module complexed with either ADP-Ca2+ (binary complex) or FMN:ADP-Mg2+ (ternary complex) have revealed that four loops of the RFK domain suffer important conformational changes induced by the ligand binding. We have selected these crystallographic models as starting point in a computational study that uses Molecular Dynamics (MD) and whose goals are to evaluate the coordination of those loop movements during the interaction of the protein with the ligands and to identify the order of binding of substrates to the enzyme. We also apply a coarse-grained description of residue-residue interactions to characterize the interactions network of the residues involved in the allosteric movements. In this way, we contribute to deepen in the knowledge of the catalytic mechanism of bacterial FAD synthetases.

[1] Herguedas B., Martínez-Júlvez M., Frago S., Medina M., and Hermoso J.A. (2010) J. Mol. Biol. 400, 218-230.


52

P 06

Mechanical versus Thermal Free Energy Landscape Analysis of a

Coarse-Grained Protein

Rafael Tapia-Rojo1,2, Sergio Arregui1,2, Juan José Mazo2,3 and Fernando Falo1,2. 1 Instituto de Biocomputación y Física de Sistemas Complejos (BIFI), Universidad de Zaragoza. 50018,

Zaragoza, Spain. 2 Dpto. de Física de la Materia Condensada, Universidad de Zaragoza. 50009 Zaragoza, Spain. 3

Instituto de Ciencia de Materiales de Aragón (ICMA), C.S.I.C., Universidad de Zaragoza.

Coarse-grained models have become a valuable tool for biomolecule modeling and the understandin of biological processes [1]. The sacrifice of some degrees of freedom by gathering groups of atoms allows the simulation of larger systems during longer timescales, compared to the more detailed all-atom simulations. In particular, proteins become a very suitable system for coarse-grained modeling, giving rise to a large variety of models that pretend to describe its complex behavior [2]. Perhaps, the central problem concerning proteins is that of protein folding. Huge effort has been devoted on understanding the mechanisms that drive this key process, either by means of massive simulations or by single molecule experiments, where a single protein is mechanically unfolded by means of an external force [3]. In any case general questions arise, such as the choice of the correct reaction coordinate or the comparison between thermal unfolding (entropy based) and mechanical unfolding, where both states have similar entropy. Here we use an off-lattice coarse-grained model where each aminoacid is reduced to a bead centered in the alpha-carbon and explicit interaction terms are considered [4]. The model accounts also for three different “flavors”: neutral, hydrophobic and hydrophilic, according to the behavior of the aminoacids in water. This model is used on a toy sequence that successfully folds into a stable structure constituted by four beta strands and whose thermal behavior has been correctly characterized [5]. We simulate the protein by means of Langevin equation at different temperatures and applying a constant force, mimicking force-clamp experiments. The output of the simulations is analyzed by choosing different reaction coordinates, such as the native contacts [6], or the radius of gyration. More sophisticated techniques are also applied, mainly Principal Component Analysis and Conformational Markov Networks [7]. Two main questions are explored. Firstly, the adequacy of each of the description levels to the specific problems we are studying. Secondly, thermal and mechanical landscapes are compared in order to find common features. Even though it is known that both processes do not have to share common characteristics, we find similar unfolding patterns in both unfolding mechanisms that can be correctly characterized by the construction of a Conformational Markov Network and its division into the basins of attraction.

[1] Noid W. G. (2013) J. Chem. Phys. 139, 090901 [2] Hue Sun C., Zhang Z., Wallin S. Liu Z. (2011) Annu. Rev. Phys. Chem. 62: 301-26 [3] Popa I. et. al. (2013) J. Am. Chem. Soc. 135 (34), 12762-12771 [4] Imparato A., Luccioli S. and Torcini A. (2007) Phys. Rev. Lett. 99, 168101 [5] Luccioli S., Imparato A. and Torcini A. (2008) Phys. Rev. E 78, 031907 [6] Best R. B., Hummer G., and Eaton W. A. (2013) PNAS. 110, 44 [7] Prada-Gracia D., Gomez-Gardeñes J., Echenique P. and Falo F. (2009) PLOS Comput. Biol. 5, 6


53

P 07 Predicted structure and function of FADS-type II protein from Listeria

monocytogenes

Inmaculada Yruela1,2, Patricia Ferreira2, Marta Martínez-Júlvez2, Bruno Contreras-Moreira1,2,3, Milagros Medina2

1 Estación Experimental de Aula Dei, Consejo Superior de Investigaciones Científicas (EEAD-CSIC), Avda. Montañana, 1005, 50059 Zaragoza, Spain. 2 Instituto de Biocomputación y Física de Sistemas Complejos (BIFI), Universidad de Zaragoza, Mariano Esquillor, Edificio I + D, Zaragoza 50018, Spain. 3 Fundación ARAID. Flavin adenine dinucleotide synthetases (FADSs) are known as a group of prokaryotic bifunctional enzymes that carry out the dual functions of riboflavin phosphorylation to produce flavin mononucleotide (FMN) and its subsequent adenylylation to generate FAD (hereafter FADS-type I). A recent work [1] using a variety of bioinformatics methods revealed that certain gram-positive pathogenic bacteria (i.e. Listeria monocytonegens, Listeria welshimeri, Lactobacillus plantarum, Bacillus cytotoxicus) contain also a variant of FADS sequences, named FADS-type II. These two types of sequences cluster together. Although the phylogenetic tree does not support that FADS-type II proteins constitute a distinct evolutionary class, their shorter and non-conserved C-terminal domains suggest them as a distinct functional group unable to produce riboflavin phosphorylation. In this work the putative structure and function of the C-terminal domain of the FADS-type II from Listeria monocytonegens (LmFADS-typeII) has been investigated. The results point out that this C-terminal domain contains a LPAxGxY conserved sequence motif with high homology with the LPASGxY consensus sequence common to proteins acting as lysozyme inhibitors, such as PliG, PliC and PliI, in gram-negative bacteria. This motif has been shown to be important for lysozyme inhibition in the PliC and PliI families, defending bacteria against the lytic action of host lysozymes [2]. In gram-positive bacteria no homology was found with lysozyme inhibitors. Interestingly, in this bacterium linage homologies were found with FMN reductases domains. A structural model for the C-terminal domain of LmFADS-type II is also proposed. [1] I. Yruela, Arilla-Luna,S., Medina,M. and B Contreras-Moreira. Evolutionary divergence of chloroplast FAD synthetase proteins. (2010) BMC Evol. Biol. 10:311.

[2] S. Leysen, L. Vanderkelen, S.D. Weeks, C.W. Michiels and S.V. Strelkov. Structural basis of bacterial defense against g-type lysozyme-based innate immunity. (2013). Cell. Mol. Life Sci. 70:1113-1122.


54

P 08

Rescuing the antiviral activity in cell culture of selected in vitro compounds against hepatitis C virus by using cyclodextrins

Rafa Calvería1, Adrian Velázquez1,2,3, Olga Abian1,4

1Institute of Biocomputation and Physics of Complex Systems (BIFI), Joint-Unit IQFR-CSIC-BIFI, University of Zaragoza, Zaragoza, Spain.

2Department of Biochemistry and Molecular and Cell Biology, University of Zaragoza, Zaragoza, Spain. 3Fundacion ARAID, Government of Aragon, Zaragoza 50018, Spain.

4Instituto Aragonés de Ciencias de la Salud (IACS)-IIS Aragón, Zaragoza, Spain; Centro de Investigación Biomédica en Red en el Área Temática de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain.

Although specific inhibitors have been approved for Hepatitis C Virus (HCV) clinical therapy very recently, resistance-associated mutations have already been reported for those drugs, compromising their long-term efficacy. Therefore, there is an urgent need for new anti-HCV agents with low susceptibility to resistance-associated mutations. NS3 protease protein has been considered a target for drug development since its identification two decades ago. Several inhibitors of this enzyme have been identified. Three of them exhibited good efficacy in vitro but they had poor efficacy in cellular assays. In order to enhance the cell uptaking of these compounds, they were complexed with γ-cyclodextrin and afterwards, their efficacy was tested using a replicon system that mimic the virus cycle in cells. Two of them increased 5 and 16 times their efficacy in comparison when they were offered as free compounds. But the most significant result came with one compound that did not show any antiviral activity in cells when it was free but its γ-cyclodextrin complexed exhibited an efficacy value concentration of 5 µM. So, the antiviral efficacy of these compounds can be improved or even rescued usingγ-cyclodextrin as carrier molecule


55

P 09

Analyzing the oxidative stress response in FurB (Zur) mutants of Anabaena PCC 7120

Violeta Calvo1, Mauro Napolitano2, Andrés González1, Ignacio Luque2 and María F. Fillat1

1 Department of Biochemistry and Molecular and Cell Biology, Faculty of Sciences and Biocomputation and Complex Systems Physics Institute (BIFI), University of Zaragoza (Spain) 2 Institute of Plant Biochemistry and Photosynthesis, CSIC and University of Sevilla (Spain)

FurB is one of the three paralogs of the Fur family in Anabaena sp. PCC 7120, where it has been shown to act as a Zur regulator [1]. It has also been demonstrated that FurB overexpression in E. coli increases cell survival against oxidative stress induced by hydrogen peroxide and that it protects DNA against ROS and DNaseI in vitro [2]. In the present study, we have analyzed different aspects of the oxidative stress response in FurB mutants of Anabaena sp. PCC 7120: a furB deletion/insertion mutant (ΔfurB) and a furB-overexpressing mutant (VCS2770FurB).

When measuring catalase activity, we found that the ΔfurB mutant presented increased activity compared to

the wild type strain, while the VCS2770FurB mutant exhibited the lowest activity. These results were consistent with those obtained by semi-quantitative RT-PCR, where we observed a higher level of expression of Mn-catalase (alr0998) in ΔfurB. We also quantified the levels of hydrogen peroxide in the strains and found that, even having the lowest catalase activity, VCS2770FurB had the lowest H2O2 content. Actually, VCS2770FurB showed the highest tolerance against hydrogen peroxide in the experiments we carried out.

Western blot analyses were also performed to study the level of expression of FurB in Anabaena sp. PCC

7120 under different environmental conditions. We observed an increase in FurB expression under high light conditions and moderate exposure to hydrogen peroxide. However, the expression decreased under low light conditions and high exposure to hydrogen peroxide, which probably damaged the protein. We also observed an increase in FurB expression during cyanobacterial growth, finding the highest amount of protein in the late exponential phase of growth.

Taken altogether these results reinforce the theory that FurB may have a protective role in Anabaena sp.

PCC 7120. That would explain the increase of catalase activity in ΔfurB (when the cells lack the protective protein FurB, there is a higher requirement of detoxifying enzymes like catalase) and under stressful situations caused by high light or hydrogen peroxide exposure. [1] Napolitano M., et al. (2012) J Bacteriol. 194(10), 2426-36.

[2] Lopez-Gomollon S., et al. (2009) Biochem J. 418(1), 201-7.


56

P 10

Study of the interaction between NtcA from Microcystis aeruginosa PCC 7806 and mcyAD promoter in the presence of amino acids: a Surface Plasmon Resonance

approach.

Laura Ceballos,1,2 Míriam Alías,2 Laura Calvo,1,2 María L. Peleato1,2

1 Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Ciencias, Universidad de Zaragoza

2 Institute for Biocomputation and Physics of Complex Systems (BIFI). Universidad de Zaragoza.

Microcystins are a non-ribosomal cyclic heptapeptides, a class of natural toxins produced by some types of cyanobacteria, which grow worldwide in fresh and brackish waters. These toxins are potent inhibitors of the catalytic subunits of serin/threonine protein phosphatase-1 (PP-1) and protein phosphatase-2A (PP-2A), which play essential roles in the reversible phosphorylation and dephosphorylation of proteins and have been involved in a large number of cellular events. Modular peptide synthases and polyketide synthases are involved in the synthesis of these toxins, as well as other enzymes and mcy operon encodes biosynthesis machinery in Microcystis aeruginosa PCC7806 [1].

NtcA is a master regulator of nitrogen metabolism in cyanobacteria belonging to the CAP/CRP family (the catabolite activator protein or cyclic AMP receptor protein). It regulates the expression of a large number of genes, especially those involved in nitrogen metabolism, as well as other many aspects of cyanobacterial metabolism, such as carbon metabolism, photosynthesis, and stress responses [2].

Previous experiments using band-shift assay (EMSA) showed the binding affinity of NtcA towards promoter regions of the microcystin gene cluster from Microcystis aeruginosa PCC 7806 [3]. The key nitrogen transcriptional regulator exhibits affinity for the two fragments of the bidirectional mcyDA promoter, as well as for promoter regions of mcyE and mcyH. To obtain further in vitro evidence of the interaction between NtcA and mcyAD promoter in the presence of amino acids, SPR (surface plasmon resonance) studies were performed using Biacore T200.

[1] Luque I., Forchhammer K. (2008) in The cyanobacteria: molecular biology, genomics and evolution, pp. 335-382. Caister Academic Press, Norfolk, U.K. p.335-382.

[2] Herrero A., Muro-Pastor A.M., Flores E. (2001) J. Bacteriol. 183, 411-425.

[3] Kuniyoshi T.M., Gonzalez A., Lopez-Gomollon S., Valladares A., Bes M.T., Fillat M.F., Peleato M.L. (2011) FEBS Lett. 585, 3921-3926.


P 11

γ-Lindane induces nirA in Microcystis aeruginosa PCC 7806, involved in the degradation of the pesticide

Laura Ceballos 1,2 , Laura Calvo1,2, Francisco Barja3, María Teresa Bes1,2, María F. Fillat1,2

and María Luisa Peleato1,2* 1Department of Biochemistry and Molecular & Cellular Biology, Faculty of Science, and the Institute for Biocomputation and 2Physics of Complex Systems (BIFI), University of Zaragoza, Pedro Cerbuna 12, 50009-Zaragoza, Spain. 3University of Genève, Microbiology Laboratory, 30 Quai Ernest-Ansermet, 1211-Genève, Switzerland. *Corresponding author: [email protected]

The extreme adaptability of some cyanobacteria makes them able to tolerate and even metabolize moderate doses of pesticides as lindane (γ-HCH). Previous results of our group showed that M. aeruginosa is highly tolerant to the pesticide lindane and its presence induces microcystin synthesis [1]. NirA is a nitrito oxidoreductase that uses ferredoxine as physiologic reductor. Nitrate is introducing into the cytoplasm and reduced to ammonia by NaR and NiR complex [2]. Different studies in Anabaena sp. PCC 7120 and Nostoc ellipsosporum showed that mRNA of nirA operon is induced and linked to a natural ability to degrade the highly chlorinated aliphatic pesticide [3-4]. Previously, Hall and college proposed cyanobacteria as an alternative in the treatment of wastewaters [5].

When effects of lindane and other pesticides are studied, ethanol solutions were used as solvent. Our results show that ethanol itself, at the usual concentrations, has important physiological effects and affects gene expression. For those reasons, solubility of lindane (with a limit of 7 mg/L) should be used.

M. aeruginosa PCC 7806 in presence of lindane showed a tendency to form bigger colonies (monitored by Scanning Electron Microscope), which can be related to an increased amount of microcystin. Gene expression analysis in presence of lindane indicated that besides changes in genes belonging to the mcy operon (Ceballos et al. 2013), furA and its antisense change their expression. The most relevant result is the fact of a marked induction of nirA gene, which can be interpreted as an indication of the pesticide degradation.

[1] Ceballos, L., Calvo L., Bes M. T., Fillat F., Peleato M. (2014). Environmental Science and Technology (En revisión).[2] Guerrero, M.G. y Lara, C. 1987. En: The Cyanobacteria. P. Fay, C. Van Baalen (Eds), Elsevier Science Publishers. Amsterdam, pp. 163-186.[3] Kuritz, T. y Wolk, C.P. (1995). Appl Environ Microbiol 61: 234-238.[4] Bueno, M., Fillat, M.F., Strasser, R.J., Maldonado-Rodriguez, R., Marina, N., Smienk, H., Gomez-Moreno, C. y Barja, F. (2004). Environ Sci Pollut Res Int 11: 98-106. [5] Hall, D.O., Markov S.A., Watanabe Y. y Rao K.K. (1995). Photosynthesis Research 46: 159-167.

mailto:[email protected]


58

P 12

Numerical Analysis of the Equilibrium and Kinetics of the Repeat Protein Gankyrin

Mauro Faccin1, Pierpaolo Bruscolini2, Alessandro Pelizzola3, Laura S. Itzhaki4

1ISI Foundation, Via Alassio 11/c, 10126 Torino, Italy.

2Departamento de Física Teórica & Instituto de Biocomputación y Física de Sistemas Complejos (BIFI), Universidad de Zaragoza, c/ Mariano Esquillor s/n, 50018, Zaragoza, Spain.

3Dipartimento di Scienza Applicata e Tecnologia, CNISM and Center for Computational Studies, Politecnico di Torino, Corso Duca degli Abruzzi 24, I-10129 Torino, Italy.

4Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, UK.

We apply a simple binary model to study the equilibrium and folding/unfolding kinetics of gankyrin, a 226-residue protein comprising seven ankyrin repeats. The latter are small helical motifs, that arrange themselves in a tandem array that stack in a linear fashion to produce elongated architectures, stabilised by short-range interactions. The size of the protein, together with its modularity, prompts for the possible existence of equilibrium and kinetics intermediates, and alternative relaxation pathways, on top of a highly complex energy landscape, most of which invisible to direct experimental observation. In this framework, numerical simulations with coarse-grained models represent a complementary tool for the interpretation of experimental results.

Thanks to the accurate treatment of the interactions, our model is able to reproduce both the equilibrium and the kinetics behavior of the protein to a good detail. Our numerical results for gankiryn support the conclusions obtained from site-directed mutagenesis experiments, about the greater stability of the N-terminal part of the chain, and the existence of two main alternative pathways, both in folding and unfolding, that develop from the N- to the C-terminal, or viceversa.

Our study highlights the complexity of repeat-protein folding that results from the symmetrical nature of their structures; at the same time, it shows that accurately designed coarse-grained models can be used to effectively reproduce and predict experimental results also in the case of medium-sized proteins, that are not easily accessible with detailed MD simulations.


59

P 13

Preliminary analyses of the interaction of heme with the Ferric Uptake Regulator of Clostridium difficile

Angela Fernández-Otal1,2, Alejandro Asensio1, Andrés González1, María F. Fillat1, Angel Lanas2 and M. Teresa Bes1.

1Department of Biochemistry and Molecular and Cell Biology, and Institute for Biocomputation and Physics of Complex Systems (BiFi), University of Zaragoza, Zaragoza, Spain. 2 Instituto Aragonés de Ciencias de la Salud (IACS), Zaragoza, Spain. Clostridium difficile has been traditionally recognized as a toxin-producing anaerobic Gram-positive bacterium responsible for antibiotic-associated colitis. The disease commonly results from a disturbance of the normal microbiota of the colon due to antibiotic therapy, colonization and/or proliferation of C difficile, and the release of toxins that cause mucosal inflammation and damage. Nowadays this pathogen is the most common infectious cause of nosocomial diarrhea, showing a steady and considerable increase in morbidity and mortality associated to severe C. difficile infections. In combination with other strategies, the identification of bioactive compounds that may specifically inactivate essential molecules of this microorganism and thereby inhibit or eradicate the infection could lead rational design of new antimicrobials. Fur (Ferric Uptake Regulator) protein is a metal-dependent transcriptional regulator responsible for controlling iron homeostasis in many prokaryotes. Furthermore, Fur mediates the expression of several virulence genes as response to the signal of environmental iron-deficient conditions that occurs into the host. Deletion or inactivation of Fur usually results in loss of viability, decrease of virulence or increase of the microbial susceptibility to environmental stresses. Therefore, Fur proteins constitute attractive targets for the development of new antimicrobial compounds. Previous studies on the FurA from the cyanobacterium Anabaena sp. PCC 7120 have shown that the protein binds heme through a cysteine-proline motif (heme regulatory motif), and this interaction disrupts the DNA-binding capacity of Fur in vitro [1]. The CP motif also occurs in the C. difficile Fur protein (CdFur), while the deletion of fur gene increase the sensitivity to oxidative stress of Clostridium strains [2]. In the present work we analyze the interaction of CdFur and heme as preliminary step to the search of bioactive compounds which resemble the inactivating binding of heme to Fur through the CP motif. CdFur punctual mutants (C51A and P52A) were generated by site-directed mutagenesis, overexpressed in Escherichia coli and purified by immobilized metal ion affinity chromatography. The biological activity of each mutant was compared with wild-type by means of electrophoretic mobility shift assays (EMSA). Interaction of each protein with heme was analyzed by differential spectroscopy, while influence of heme in DNA-binding capacity of each protein was followed by EMSA.

[1] Hernández, J. A., Peleato, M. L., Fillat, M.F. and Bes, M. T. (2004). Heme binds to and inhibits the DNA-binding activity of the global regulator Fur of cyanobacterium Anabaena sp. PCC 7120. J. Mol. Biol. 577, 35-41.

[2] Vasileva, D., Janssen, H., Hönicke, D., Ehrensreich, A. and Bahl, H. (2012). Effect of iron limitation and fur gene inactivation on the transcriptional profile of the strict anaerobe Clostridium acetobutylicum. Microbiology. 158, 1918-1929.


60

P 14

RNAseq analysis of differentially expressed genes between two barley genotypes with contrasting yield under drought

María Jesús García-Pereira1,*,Carlos P Cantalapiedra1,*, Ana M Casas1, Ernesto Igartua1, Bruno Contreras-

Moreira1,2

1 Dpt of Genetics and Plant Production, Estación Experimental de Aula Dei, CSIC, Av. Montañana 1005,

Zaragoza 50059, Spain

2 Fundación ARAID, Zaragoza, Spain

* These authors contributed equally to this work

The traditional cultivars and landraces of the Spanish Barley Core Collection [1] harbour genetic variability of potential interest for breeding elite varieties adapted to Mediterranean environments. Here we compare in vivo gene expression profiles of two contrasting cultivars when grown under drought-stress: SBCC073, a winter landrace with high yield under drought conditions, and the elite cultivar Scarlett, a European cultivar that performs poorly with low water supply. Plants of both genotypes were cultivated under different watering treatments. RNA was extracted from several tissues for subsequent library preparation and high throughput sequencing of 2-3 biological replicates per genotype/treatment combination with Illumina HiSeq 2000. A total of 1.2 billion 2x100 bp reads were obtained, which were subject to removal of adapters and low-quality sequences. As the only available references are the genomic sequences of European and American spring barley cultivars Morex, Barke and Bowman [2], reference transcriptomes of SBCC073 and Scarlett were also sequenced and assembled using Trinity [3]. After removing chimeras and other unlikely constructs, nearly 298941 transcripts were validated by stringent alignments (coverage ≥95% and identity ≥80%) to barley and other Triticeae sequences. Gene and isoform quantification was performed with RSEM [4] and differential expression analyses with edgeR [5]. Preliminary results suggest a total of 4262 differentially expressed young inflorescence mRNA isoforms between Scarlett and SBCC073, of which 957 can be mapped to high confidence barley genes. This study reveals molecular details of the adaptation of Mediterranean barley genotypes to drought.

[1] Igartua E., Gracia M.P., Lasa J.M., Medina B., Molina-Cano J.L., et al. (1998) Genet. Resour. Crop. Evol. 45, 475-482.

[2] IBSC International Barley Genome Sequencing Consortium. (2012) Nature 491:711-716.

[3] Haas B.J., Papanicolaou A., Yassour M., Grabherr M., Blood P.D., et al. (2013) Nat. Protoc. 8(8), 1494-512.

[4] Li B. and Dewey C.N. (2011) BMC Bioinformatics 12, 323.

[5] Robinson M.D., McCarthy D.J. and Smyth G.K. (2010) Bioinformatics 26, 139-140


61

P 15

Bioinformatic prediction and experimental validation of novel FurA-regulated genes in Anabaena sp. PCC 7120

Andrés González1, Vladimir Espinosa Angarica1,2, Javier Sancho1,2, and María Fillat1

1 Departamento de Bioquímica y Biología Molecular y Celular e Instituto de Biocomputación y Física de Sistemas Complejos (BIFI), Universidad de Zaragoza.

2 Unidad Asociada BIFI-IQFR (CSIC).

Computational approaches have proven quite useful for identifying cis-acting regulatory elements that function as binding sites for transcription factors [1]. These strategies have been successfully used to expand the knowledge of multiple regulons, from microorganisms to humans, including those associated to several Fur proteins [2,3]. In the present study, we scan the Anabaena sp. PCC 7120 genome in the search for FurA putative binding sites matching the position weight-matrix generated from a data set comprised of 8 footprinted sites [4,5]. Predicted FurA binding sites were identified upstream of 215 genes belonging to diverse functional categories including iron homeostasis, photosynthesis and respiration, heterocyst differentiation, oxidative stress defences, and light-dependent signal transduction mechanisms, among others. Our weight-matrix-based prediction model proved to be quite effective at discerning FurA boxes from non-cognate sequences, while EMSA experiments confirmed in vitro specific binding of the regulator to selected 20% of predicted targets with known function. Gene expression analyses further support the dual role of FurA as transcriptional regulator, acting both as repressor and activator of gene expression. In either case, the in vivo FurA-mediated regulation seems to be dependent of the environmental iron availability as well as the intracellular redox status. Thus, FurA appears to couple iron homeostasis and oxidative stress to major physiological processes in cyanobacteria.

References:

[1] Bulyk, M.L. (2003) Genome Biol. 5, 201.

[2] Quatrini, R., Lefimil, C., Veloso, F.A., Pedroso, I., Holmes, D.S., and Jedlicki, E. (2007) Nucleic Acids Res. 35, 2153-2166.

[3] Da Silva, J.F., Braz, V.S., Italiani, V.C., and Marques, M.V. (2009) Nucleic Acids Res. 37, 4812-4825.

[4] Hernández, J.A., López-Gomollón, S., Muro-Pastor, A., Valladares, A., Bes, M.T., Peleato, M.L., and Fillat, M.F. (2006) Biometals. 19, 259-268.

[5] González, A., Bes, M.T., Valladares, A., Peleato, M.L., and Fillat, M.F. (2012) Environ Microbiol. 14, 3175-3187.


62

P 16

QM/MM methods in the analysis of the mechanisms of hydride transfer processes between flavoreductases and pyridine nucleotides

Isaias Lans1, Edina Rosta2, Gerhard Hummer3, José M. Lluch4, Àngels González-Lafont4, Mireia Garcia-Viloca4,

Milagros Medina1

1 Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Ciencias, and BIFI-Joint Unit BIFI-IQFR (CSIC), Universidad de Zaragoza, Spain 2 Department of Chemistry, King’s College London, UK 3 Max-Planck-Institut für Biophysik 4 Departament de Química and Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Spain.

During photosynthesis ferredoxin-NADP+ reductase (FNR) catalyses the electron transfer from ferredoxin to NADP+ via its FAD cofactor. The final hydride transfer event between FNR and the nucleotide is a reversible process. Two different transient charge-transfer complexes form prior to and upon hydride transfer, FNRrd-NADP+ and FNRox-NADPH, and regardless of the hydride transfer direction. Experimental structures of the FNRox:NADP+ interaction suggested a series of conformational rearrangements that might contribute to attain the catalytically competent complex [1]. A Molecular Dynamics (MD) theoretical approach was used to provide a putative organization of the active site that might represent a structure close to the transient catalytically competent interaction of Anabaena FNR with its coenzyme, NADP+. Using this structure, fully microscopical simulations of the hydride transfer processes between Anabaena FNRrd/FNRox and NADP+/H, accounting also for the solvation, were carried out. A dual level QM/MM hybrid approach was used to describe the potential energy surface of the whole system. MD calculations using the finite-temperature string method with the WHAM method provided the potential of mean force of the hydride transfer process. The results confirm that the structural model of the reactants evolves to a catalytically competent transition state through very similar free energy barriers for both the forward and reverse reactions [2], in good agreement with the hydride transfer experimental rate constants reported in this system. This theoretical approach additionally provides subtle structural details of the mechanism in wild-type FNR. This approach appears as a good tool to implement in the study of the mechanisms of other flavoreductases depending on pyridine nucleotides.

[1] Peregrina J.R., Lans I., and Medina M. (2012) Eur. Biophys. J. 41, 117-128.

[2] Lans I., Medina M., Rosta E., Hummer G., Garcia-Viloca M., Lluch J.M., González-Lafont A. (2012) J. Am. Chem. Soc. 134, 20544-20553.


63

P 17

Rett Syndrome: Structural and Functional Characterization of MeCP2 and Search for Pharmacological Chaperones

Pilar Mª Lanuza1, Sonia Vega1, Olga Abian1,2,3, Adrian Velazquez-Campoy1,2,4

1Institute of Biocomputation and Physics of Complex Systems (BIFI), Joint-Unit IQFR-CSIC-BIFI, University of Zaragoza, Zaragoza, Spain

2Department of Biochemistry and Molecular and Cell Biology, University of Zaragoza, Zaragoza, Spain

3Instituto Aragonés de Ciencias de la Salud (IACS)-IIS Aragón, Zaragoza, Spain; Centro de Investigación Biomédica en Red en el Área Temática de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain

4Fundacion ARAID, Government of Aragon, Zaragoza 50018, Spain

Rett syndrome is an X-linked neurodevelopmental disorder affecting 1/10000 live female births and caused by mutations in MeCP2 (methyl CpG binding protein 2) resulting in defective protein. Patients are heterozygous for the mutated allele, and although there is some weak correlation between disease severity and MeCP2 mutations, the most influential factor is X-chromosome inactivation pattern. Rett syndrome represents the main cause of mental retardation in girls. An initial period of apparent normal development is followed by regression with manifestation of many autistic features, as well as loss of acquired language and motor skills. Next, stereotypic hand movements and gait abnormalities are accompanied by numerous other problems. Rett syndrome is considered to be the result from disruption of postnatal and experience-dependent synaptic plasticity.

MeCP2 is a multifunctional nuclear protein involved in neuronal differentiation and maturation. It is organized in 6 domains with abundant unstructured regions constituting the structural and energetic basis for establishing multiple high-to-moderate affinity transient interactions with DNA and other proteins. Mutations in MeCP2 result in a defective protein with reduced stability, folding defects, and diminished DNA binding affinity. A great part of these mutations are located in the methyl binding domain (MBD).

Importantly, Rett syndrome is not a degenerative disorder, but it can be reverted by restoring MeCP2 function. Thus, the development of pharmacological chaperones rescuing the activity of defective mutants with reduced structural stability constitutes an appropriate therapeutic approach.

We have initiated a biophysical study of MeCP2 (MBD and full length protein) intended to: 1) characterize the structural and functional role of unstructured regions in this modular multifunctional protein; 2) provide valuable information for starting an experimental screening procedure for the identification of ligands stabilizing the quasi-native MeCP2 conformation and rescuing the activity in defective mutants associated with Rett syndrome.


64

P 18

Phylogeny and biogeography of the grass model genus Brachypodium

Diana López-Alvarez1, Maria Luisa López-Herranz1, Pilar Catalan1

1 Department of Agriculture and Environmental Sciences, High Polytechnic School of Huesca, University of Zaragoza, Huesca, Spain

Brachypodium has been recognized as a key model genus for the grasses based on its biological and genomic attributes and its evolutionary history [1, 2]. It contains ~15-18 species with an unusually high level of variation in chromosome number and ploidy. This diversity was a subject of phylogenetic interest long before B. distachyon was proposed as an experimental model [1, 3]. Advanced genomic and cytogenetic studies suggest a complex reticulate history for most of its representatives, involving different interspecific hybridizations between annual and perennial species followed by subsequent allopolyploidizations [4].

A dated phylogeny and a robust biogeographic model for Brachypodium were obtained after a broad survey of all the worldwide distributed species of the genus Combined bayesian phylogenetic analysis based on two cloned nuclear (ETS, ITS) and two plastid (ndhF, trnTL) genes resulted in a Brachypodium species-tree showing the early divergence of relictual perennials (B. boissieri, B. mexicanum) and annuals (the B. distachyon complex) and a later split of the recently evolved core perennial clade (11 taxa). Bayesian dating analysis (Beast) and ancestral area reconstructions (DEC models) support an early-Miocene origin of the Brachypodium ancestor in the circumMediterranean region, followed by successive dispersals to America, Africa and SE Asia in mid-Miocene, Pliocene and Pleistocene times, respectively. These analyses have set the stage for high definition investigation of the unusual genomic diversity and evolutionary relationships in Brachypodium through next generation sequencing approaches.

[1] Catalán P, Olmstead RG (2000) Phylogenetic reconstruction of the genus Brachypodium P.Beauv. (Poaceae) from combined sequences of chloroplast ndhF gene and nuclear ITS. Plant Systematics and Evolution 220: 1-19

[2] Mur LA, Allainguillaume J, Catalan P, Hasterok R, and Jenkins G, et al. (2011) Exploiting the Brachypodium Tool Box in cereal and grass research. New Phytol. 191, 334-347.

[3] Catalan P, Muller J, Hasterok R, Jenkins G, Mur LA, et al. (2012) Evolution and taxonomic split of the model grass Brachypodium distachyon. Ann Bot. 109, 385-405.

[4] Wolny E, Lesniewska K, Hasterok R, Langdon T (2010) Compact genomes and complex evolution in the genus Brachypodium. Chromosoma 120: 199-212.


65

P 19

FurA binds to iron boxes sequentially using bending to promote the recruitment of new molecules to modulate the regulation in Anabaena

María Carmen Pallarés1, Laura Botello-Morte2, Carlos Marcuello1, María Francisca Fillat2, Anabel Lostao1,3, ‡

1 Laboratorio de Microscopías Avanzadas (LMA), Instituto de Nanociencia de Aragón (INA), Universidad de Zaragoza, 50018 Zaragoza, Spain

2 Department of Biochemistry and Molecular and Cell Biology and Institute for Biocomputation and Complex Systems Physics (BiFi), Universidad de Zaragoza, 50009 Zaragoza, Spain 3 Fundación ARAID, Spain

Ferric uptake regulators are involved in the control of a variety of processes in most prokaryotes. Although it is assumed that these regulators bind their DNA targets as a dimer, the way in which this interaction occurs remains unknown. We have focused on the FurA regulator from the cyanobacterium Anabaena sp. PCC 7120. To assess the molecular mechanism by which FurA specifically binds to “iron boxes” in PfurA, we examined the topology arrangement of FurA–DNA complexes by atomic force microscopy. Previously the association pattern of the regulator in different redox environments was also analyzed at the single molecule level [1]. Interestingly, FurA–PfurA complexes exhibit several populations, in which one is the predominant and depends clearly on the regulator/promoter ratio on the environment. Those results together with EMSA and other techniques suggest that FurA binds PfurA using a sequential mechanism: (i) a monomer specifically binds to an “iron box” and bends PfurA; (ii) two situations may occur, that a second FurA monomer covers the free ”iron box" or that joins to the previously used forming a dimer which would maintain the DNA kinked; (iii) trimerization in which the DNA is unbent; and (iv) finally undergoes a tetramerization; the next coming molecules cover the DNA strands unspecifically.

The analysis was completed by studying the role that previously formed FurA oligomeric species plays in promoter binding steps. The double variant FurAC141S:C144S organizes mainly as oligomeric species from low concentrations. The triple variant FurAC133S:C141S:C144S only dimerized in a very low extension, 11 %, versus the 80 % exhibited by the wild-type protein, in absence of DNA. On the other hand, it was observed a majority of monomers of this variant bound to PfurA, appearing also few dimers, trimers and tetramers; this species do not introduce bending.

In summary, the bending appears when an “iron box" is bound to one or two molecules and decreases when both "iron boxes" are covered. These results suggest that DNA bending contributes at the first steps of FurA repression promoting the recruitment of new molecules resulting in a fine regulation in the Fur-dependent cluster associated genes [2].

[1] Lostao A., Peleato M.L. Gomez-Moreno C., Fillat M.F. (2010) BBA-Proteins 1804, 1723–1729.

[2] Pallarés M.C., Marcuello C, Botello-Morte L., González A., Fillat M.F., Lostao A. BBA-Proteins, in press. DOI 10.1016/j.bbapap.2014.01.005


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P 20

Binding of the second molecule of coenzyme to the Apoptosis Inducing Factor: Docking analysis and sequence identification of disordered regions

Raquel Villanueva1, Patricia Ferreira1, Beatriz Herguedas1, Marta Martínez-Júlvez1, Inmaculada Yruela1,2, Milagros Medina1.

1 Department of Biochemistry and Molecular and Cellular Biology and Institute for Biocomputation and Physics of Complex Systems (BIFI), Universidad de Zaragoza, Zaragoza, Spain. 2 Estación Experimental Aula Dei, Consejo Superior de Investigaciones Científicas (EEAA-CSIC), Zaragoza, Spain.

The Apoptosis Inducing Factor (AIF) is a mitochondrial flavoenzyme with a double function: in mitochondria it has a NADH dependent oxido-reductase activity through its FAD cofactor [1], and after an apoptotic stimulus it is liberated to the cytosol and translocated to the nucleus where it induces typical caspase independent chromatinolysis (partial chromatin condensation and 50 kb DNA fragmentation) [2]. The redox state of the protein has been suggested by some authors to modulate both functions [3, 4, 5].

Resolution of the crystallographic structure of the reduced human AIF in complex with NAD+ reveals two NAD+ binding sites, one of them described for the first time by our group. This new site might be relevant in the modulation of both activities of the protein, since human mutants at this site have been related with severe myophaties. Despite the fact that this site was not described in the previously reported structure of the murine enzyme in complex with the coenzyme, the docking analysis here presented predicts that binding of the second NAD+ molecule in this structure will take place similarly to that found in the human enzyme. To further characterize the environment of this newly discovered site, which gets disordered upon coenzyme binding, we have analyzed the occurrence of intrinsic disordered regions from the protein aminoacid sequence. This analysis suggests a disordered region coincidental with a region seen in the crystallographic structure, and which our crystal structure shows gets disordered upon coenzyme binding and protein reduction.

[1] Maté M.J., Ortiz-Lombardía M., Boitel B., Haouz A., Tello D., Susin S.A., Penninger J., Kroemer G., and Alzari P.M. (2002) Nat. Struct. Biol. 9, 442-446.

[2] Susin S.A., Lorenzo H.K., Zamzami N., Marzo I., Snow B.E., Brothers G.M., Mangion J., Jacotot E., Costantini P., Loeffler M., Larochette N., Goodlett D.R., Aebersold R., Siderovski D.P., Penninger J.M., and Kroemer G. (1999) Nature. 397, 441-446.

[3] Sevrioukova I.F. (2011) Antioxid. Redox Signal. 14, 2545-2579.

[4] Sevrioukova I.F. (2009) J. Mol. Biol. 390, 924-938.

[5] Churbanova IY, Sevrioukova IF. (2008) J. Biol. Chem. 283, 5622-5631.


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P 21

Dances with Spin-Glasses: starring Janus

S. Perez-Gaviro1,2 (for the Janus Collaboration: http://bifi.es/scp)

1 Instituto de Biocomputación y Fisica de Sistema Complejos (BIFI) Zaragoza, Spain.

2 Fundación ARAID, Diputación General de Aragón, Zaragoza, Spain.

The FPGA-based Special Purpose Computer Janus [1,2] was designed and developed as a multipurpose reprogramable supercomputer some time ago. During these years, Janus has been focused on the study and simulation of spin glasses, paradigm of complex systems. Indeed it has revealed as a very fruitful scientific computer for studying these disordered systems, reaching simulation times up to 0.1 seconds of an experiment for very large lattices and low temperatures, or finding evidences for a finite phase transition in the Edwards-Anderson model in a magnetic field, among other important results.

Encouraged by the good results obtained so far, the Janus Collaboration decided to go an step further developing and designing the new generation Janus dedicated computer, named JanusII [3]. In this presentation I will introduce both supercomputers, Janus and JanusII, explaining their internal architectures and the way we profit by their resources and possibilities for the study of spin glasses. I will also discuss some of the last spin glass results achieved with Janus.

[1] Janus Collaboration: F. Belletti et al., Computer Physics Communications 178 (3), p.208-216, (2008).

[2] Janus Collaboration: F. Belletti et al., Computing in Science & Engineering 11-1, 48-58 (2009).

[3] Janus Collaboration: M. Baity-Jesi, et al., arXiv:1310.1032 (accepted in for publication Computer Physics Communications)


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P 22

Dynamical Resilience and Activity Patterns of Scale-Free Neural Networks

Pablo Piedrahita1, 2, Juan José Mazo2, Mario Floría1, 2 and Yamir Moreno1

1 Instituto de Biocomputación y Física de Sistemas Complejos, Universidad de Zaragoza, Zaragoza 50018, Spain

2 Departamento de Física de la Materia Condensada, Universidad de Zaragoza, Zaragoza 50009, Spain

We study the dynamics of integrate-and-fire excitable elements on top scale-free topologies. We show that for small network sizes, there are irregular global signals, but when larger networks are considered a transition to periodic behavior occurs. These regular patterns are in the high-frequency domain as the result of, what we call, saturation effect, which is in turn a consequence of both topology (hubs) and high amplitude (homogeneous) pulses. In order to avoid saturation and enhance periodic activity, we introduce a relation between topology and dynamics by linking pulse amplitudes to nodes degree (heterogeneity), which leads to global coherent oscillations regardless of the size of the network. Finally, we explore to what extent it is possible to control the signal of the ongoing dynamics as well as the dynamical robustness of the systems (in terms of its activity) when a damage of the network is simulated.


P 23

A hypothetical concanavalin A-like protein binds to mcy bidirectionalpromoter in Microcystis aeruginosa PCC 7806 assay

Laura Ceballos1,2, María Teresa Bes1,2, María F. Fillat1,2 and María Luisa Peleato 1,2*

1Department of Biochemistry and Molecular & Cellular Biology, Faculty of Science,and the Institute for Biocomputation and 2Physics of Complex Systems (BIFI),University of Zaragoza, Pedro Cerbuna 12, 50009-Zaragoza, Spain. *Correspondingauthor: [email protected]

Microcystin synthesis is an inducible event regulated by factors that are not completelydefined because literature is confusing and contradictory. mcy operon encodes themicrocystin synthetase gene cluster in Microcytis aeruginosa PCC 7806 and our groupdescribed its regulation by two transcriptional regulators, Fur (Ferric Uptake regulator)and NtcA [1-2]. Fur proteins are a family of global transcriptional regulators whichresponds to iron availability, while NtcA is a master regulator of nitrogen metabolism incyanobacteria belonging to the CAP/CRP family (the catabolite activator protein orcyclic AMP receptor protein).

The complexity of microcystin synthesis regulation suggests that more proteins could beinvolved in regulatory processes. Using a DNA pull-down assay we try to find otherproteins with the potential ability to bind mcyD promoter. The bidireccional mcyADpromoter was divided into two fragments (due to its length), a 438 bp mcyA upstreamsequence and a 331 bp mcyD gene upstream sequence. Both of them contains putativeFur and NtcA boxes, and had been observed DNA-protein complexes with the twomentioned transcriptional regulators by electrophoretic mobility shift assay (EMSA)[1,3]. Each of the two fragments of mcyD biotinilated promoter was immobilized on100 μl of streptavidin beads and the complexes were visualised by electrophoresispolyacrylamide denaturing gels. Bands were analysed by mass spectroscopy. We foundthree different proteins with promoter affinity and the identification of the proteins didnot included new transcriptional regulators; however, the amount of such type ofproteins could be out of our detection limit. Among others, we found a hypotheticalprotein with adhesive properties, similar to concanavalin A-like. This protein could beplaying a similar role to a lectin.

[1] Martin-Luna, B., Sevilla E, Hernández JA, Bes MT, Fillat MF & Peleato ML.(2006). Phytochemistry, 67(9): p. 876-81.[2] Kuniyoshi T.M., Gonzalez A., Lopez-Gomollon S., Valladares A., Bes M.T., FillatM.F., Peleato M.L. (2011) FEBS Lett. 585, 3921-3926.[3] Ginn, H. P., Pearson, L. A., Neilan, B. A. (2010). Appl Environ Microbiol. 76(13),4362-8.

mailto:[email protected]


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List of participants

Last Name Name Institution/Company Country E-mail

Abian Olga IACS-IIS ARAGON Spain [email protected]

Alías Niño Míriam BIFI-Universidad de Zaragoza

Spain [email protected]

Alonso Jose Luis Universidad de Zaragoza Spain [email protected]

Alvarez Raquel BIFI Spain [email protected]

Antoli Beatriz Universidad de Zaragoza Spain [email protected]

Arenas Alex URV Spain [email protected]

Arregui Sergio BIFI / Universidad de Zaragoza


Arruebo Maria Instituto Aragonés De Ciencias De La Salud (IACS)


Artacho Emilio Ikerbasque Spain [email protected]

Baity Jesi Marco Universidad Complutense de Madrid


Bergues Pupo Ana Elisa Universidad de Zaragoza Spain [email protected]

Bes María Teresa Universidad de Zaragoza Spain [email protected]

Borau Carlos University of Zaragoza Spain [email protected]

Botello-Morte Laura University of Zaragoza Spain [email protected]

Brey Abalo J. Javier University of Sevilla Spain [email protected]

Broset Blasco Esther Universidad de Zaragoza Spain [email protected]

Bruscolini Pierpaolo University of Zaragoza Spain [email protected]

Calvo Violeta University of Zaragoza Spain [email protected]


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Carloni Paolo Forschungszentrum Jülich GmbH, RWTH Aachen University

Germany [email protected]

Carro Aramburu

Juan Centro de Investigaciones Biológicas- CSIC


Carrodeguas José BIFI. Universidad de Zaragoza


Castro Alberto ARAID / BIFI Spain [email protected]

Cauhe Elisa BIFI Spain [email protected]

Ceballos Laita Laura Universidad de Zaragoza Spain [email protected]

Clavería Rafael BIFI Spain [email protected]

Clemente-Gallardo

Jesús Universidad de Zaragoza Spain [email protected]

Contreras-Moreira

Bruno Estación Experimental de Aula Dei-CSIC


Cozzo Emanuele BiFi [email protected]

Dopazo Joaquin Centro de Investigación Pŕicipe Felipe, Valencia


Duch Jordi Universitat Rovira Virgili Spain [email protected]

Echenique-Robba

Pablo Consejo Superior de Investigaciones Científicas (CSIC)


Faccin Mauro ISI Foundation Italy [email protected]

Falo Fernando BIFI- University of Zaragoza


Fernandez Otal Angela IACS Spain [email protected]


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Ferreira Neila Patricia Universidad de Zaragoza Spain [email protected]

Ferrer Marco Alfredo BIFI Spain [email protected]

Fillat María F. University of Zaragoza-BIFI


Galano Juan José BiFI/Universidad de Zaragoza


Garcia Alberto ICMAB-CSIC Spain [email protected]

García Pereria María Jesús Estación Experimental de Aula Dei, CSIC


Garma Leonardo Biocenter Oulu and the University of Oulu

Finland [email protected]

Gil Narvion Jose Miguel BIFI Spain [email protected]

Gil Sepúlveda Victor Alejandro

Barcelona Supercomputing Center


Giner Gracia Arturo BIFI-UNIZAR Spain [email protected]

Gómez Sergio Universitat Rovira i Virgili Spain [email protected]

González Andrés University of Zaragoza Spain [email protected]

Gracia Carlos BIFI Spain [email protected]

Hernandez Ruiz

Cristina BIFI Spain [email protected]

Hess Wolfgang University of Freiburg Germany [email protected]

Hurtado-Guerrero

Ramón BIFI/Universidad de Zaragoza


Ibáñez Mari Carmen Ibercivis Spain [email protected]

Ibar Jaime BIFI Spain [email protected]

Janke Wolfhard Universität Leipzig Germany [email protected]


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Khalil Rodriguez

Nagi Universidad de Extermadura


Lans Vargas Isaias UAB Spain [email protected]

Lanuza Pilar Mª BIFI Spain [email protected]

Latorre Muro Pedro Universidad de Zaragoza Spain [email protected]

Lopez-Gomollon

Sara EEAD-CSIC Spain [email protected]

López-Pérez Diana University of Zaragoza Spain [email protected]

Losilla Anadón Guillermo BIFI-UNIZAR Spain [email protected]

Mareschal Michel ZCAM-ARAID-BIFI Spain [email protected]

Martínez-Júlvez

Marta University of Zaragoza Spain [email protected]

Martinez-Olivan

Juan BIFI Spain [email protected]

Medina Milagros Universidad de Zaragoza Spain [email protected]

Meloni Sandro Universidad de Zaragoza Spain [email protected]

Monasson Remi CNRS and Ecole Normale Superieure

France [email protected]

Moreno Yamir Universidad de Zaragoza, Instituto BIFI


Nakajima Chihiro WPI-AIMR, Tohoku University

Japan [email protected]

Ordejon Pablo J. Catalan Institute Of Nanotechnology


Orozco Modesto IRB Barcelona - UB. Spain [email protected]

Pagonabarraga Ignacio Universitat de Barcelona Spain [email protected]


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Peleato María Luisa Universidad de Zaragoza Spain [email protected]

Perez Ruben Universidad Autonoma de Madrid


Perez-Gaviro Sergio ARAID / BIFI Spain [email protected]

Piedrahita Salom

Pablo BIFI Spain [email protected]

Preatoni Roberto LINK ENGINEERING SRL

Italy [email protected]

Procaccia Itamar The Weizmann Institute of Science

Israel [email protected]

Rivero Alejandro Universidad de Zaragoza Spain [email protected]

Roche Stephan Catalan Institute of Nanoscience and Nanotechnology-ICN2


Romero-García Javier Institut Químic de Sarrià Spain [email protected]

Rubio Angel Universidad del Pais Vasco Spain [email protected]

Ruiz Gonzalo Bifi Spain [email protected]

Ruiz-Montero Maria J. University of Sevilla Spain [email protected]

Sancho Javier UNIZAR Spain [email protected]

Sandri Mauro LINK ENGINEERING SRL

Italy [email protected]

Santos Patricia BIFI Spain [email protected]

Sanz Joaquín BIFI and University of Zaragoza


Sebastián María BIFI ??? Spain [email protected]


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Tapia-Rojo Rafael BIFI-Universidad de Zaragoza


Tarancon Lafita

Alfonso BIFI Spain [email protected]

Valero Gonzlaez

Jessika BIFI Spain [email protected]

Valles Ruben BIFI Spain [email protected]

Vega Sonia Institute BIFI Spain [email protected]

Velazquez-Campoy

Adrian Institute BIFI Spain [email protected]

Vergara Larrayad

Yolanda IUI BIFI. Universidad de Zaragoza


Vidal Isabel BIFI Spain [email protected]

Vilhena Guilherme Consejo Superior de Investigaciones Científicas - CSIC


Villanueva Llop

Raquel University of Zaragoza-BIFI


Yruela M. Inmaculada

CSIC Spain [email protected]

VI INTERNATIONAL CONFERENCE · PDF fileWelcome to VI International Conference BIFI2014, ... The relevance of combining computations with experiments for these systems will be ... SPM

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