Poster Abstracts for Category L: Simulation & system dynamics Poster L04 Morphogen Gradient Formation in a Complex Environment: An Anomalous Diffusion Model Gil Hornung, Brian Berkowitz, Naama Barkai Weizmann Institute of Science Abstract: Cell patterning during development requires diffusion of morphogen proteins through the extracellular matrix. Current models assume morphogen diffusion is Fickian. Nonetheless, this assumption disregards the complexity of extracellular environment. Here we investigate models that incorporate non-Fickian, i.e. anomalous, transport and discuss their novel and surprising properties. We further provide criteria to distinguish experimentally between Fickian and anomalous modes of morphogen transport. Contact: gil.hornung [at] weizmann.ac.il Keywords: Morphogens, Anomalous diffusion, CTRW, FRAP Poster L05 Non Genetic Individuality in Host-Phage Interaction Sivan Pearl (1,2), Chana Gabay (2), Amos Oppenheim (1), Nathalie Q. Balaban (2) (1) Department of Molecular Genetics and Biotechnology, The Hebrew University-Hadassah Medical School; (2) Racah Institute of Physics, The Hebrew University, Jerusalem, Israel Abstract: A small but clinically significant fraction of bacteria population survives extensive antibiotic treatments, a phenomenon termed persistence. We established an experimental system to analyze cell persistence in the lytic development of bacteriophage lambda upon thermal treatment of lysogenic cells. Single cell measurements and quantitative analysis reveal non-genetic individuality in the response to phage induction. Our results suggest that persistence might be a general mechanism for the co-survival of bacteria and phages. Contact: sivanpearl [at] gmail.com Poster L06 LexA Repressor - DNA Model, Binding Characteristics Matej Butala (1), Milan Hodoscek (2), Darja Zgur-Bertok (1) (1) Biotechnical Faculty, University of Ljubljana; (2) National Institute of Chemistry, University of Ljubljana Abstract: On the basis of crystal structure of LexA mutant, a model of the LexA dimer bound to the recA operator as well as relevant biochemical data we constructed a 3D model of two LexA dimers bound to the colicin K operator. LexA - DNA structural dynamics simulation was carried out with CHARMM. Model elucidates how two LexA dimers when bound to two overlapping operators avoid steric clashes and whether LexA dimers cause DNA bending at 22 and 37 oC. As colicin A is not thermoregulated a model of the colicin A activity gene, caa operator was also prepared and compared with the cka operator. Contact: matej.butala [at] bf.uni-lj.si Keywords: LexA, DNA Binding, Molecular Dynamics Poster L07 Continuous Time Markov Networks Tal El-Hay (1), Nir Friedman (1), Daphne Koller (2), Raz Kupferman (3) (1) School of Computer Science, The Hebrew University; (2) Department of Computer Science, Stanford University; (3) Institute of Mathematics, The Hebrew University Abstract: Continuous Time Markov Networks (CTMNs) is a representation language that represents continuous-time dynamics of complex system, particularly appropriate for modeling biological and chemical systems. In this language, we introdue the dynamics of the process as an interplay between two forces: the tendency of each entity to change its state and a global fitness or energy function of the entire system, which we capture by a compact graphical model that encodes the fitness of different states. One of the potential applications for CTMNs is modeling co-evolution of amino-acids in proteins. Contact: tale [at] cs.huji.ac.il Keywords: Dynamic Models, Complex Systems, Fitness Poster L08 Molecular Dynamics Simulation for the Complete Entry of Fatty Acid-Ligand of Toad Liver FABP through the Portal Region Yossi Tsfadia (1), Jonathan Kadmon (2), Anna Seltzer (1), Ran Friedman (3), Esther Nachliel (3), Menachem Gutman (3) (1) The George S. Wise Faculty of Life Sciences, Tel Aviv University; (2) Department of Physics, The Faculty of Exact Sciences, Tel Aviv University; (3) Department of Biochemistry, The Faculty of Life Sciences, Tel Aviv University Abstract: Fatty acid binding proteins are intra cellular proteins widely spread in organisms. The mechanism for the entry of the ligand to the interior binding site is unknown. In this study, we report for the first time, the primary results of a molecular dynamic simulation, which gives a description for the complete penetration of palmitate anion into the binding site. The analysis of the binding interactions shows that the driving forces for the penetration are the LJ interactions, while the stabilization comes from the electrostatic attraction between the anion and the inner residues of the protein. Contact: yossit [at] tauex.tau.ac.il Keywords: Molecular Dynamics Simulations, FABP, ALBP Poster L09 Visualization and Modelling of Moving Biomolecules: A New Approach Based on Professional 3D Animation Software Yuri Porozov (1,2), Raluca Andrei (1,2), Monica Zoppe' (1) (1) Laboratory of Gene and Molecular Therapy, Institute of Clinical Physiology, CNR, Pisa; (2) Laboratory of Molecular Biology, Scuola Normale Superiore Abstract: Vast amount of knowledge is available on structure, shapes and movements of cellular constituents and their interactions, obtained through biochemical, genetic and structural studies, microscopy etc. Except live microscopy, most experimental techniques give results in the form of fixed-frame pictures or collective results, often difficult to interpret in terms of dynamic deployment of single events. We represent data imported from pdb in 3D animation using Maya/Autodesk and animate protein movements in virtual space, according to information and rules from physics, chemistry and biochemistry. Contact: porozov [at] sns.it Keywords: Protein, Simulation, Movement, Visualization Poster L10 Protein Recognition Processes: The "Cysteine Synthase" Complex Anna Feldman-Salit (1,2), Domantas Motiejunas (1), Razif Gabdoulline (1), Markus Wirtz (3), Rudiger Hell (3), Rebecca Wade (1) (1) EML Research gGmbH, Heidelberg; (2) University of Heidelberg (IWR); (3) Heidelberg Institute of Plant Sciences Abstract: Cysteine biosynthesis in plants and bacteria involves a bienzyme "cysteine synthase" (CS) complex. The biological function of the CS is still poorly understood. It is composed of the enzymes Serine-Acyl-Transferase (SAT) and O-Acetyl-Serine-(Thiol)-Lyase (OAS-TL). We are investigating the complexation of CS in Arabidopsis thaliana by applying Brownian and Molecular Dynamics. Contact: anna.feldman-salit [at] eml-r.villa-bosch.de Keywords: Cysteine Synthase, CS, SAT, OAS-TL, Cysteine Poster L11 Modeling Natural Killer Cell Development and Repertoire Formation Mali Salmon-Divon (1), Sofia Johansson (2), Maria Johansson (2), Marjet Elemans (1,2), Petter Hoglund (2), Ramit Mehr (1,2) (1) Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel; (2) Tumor Biology Center (MTC), Karolinska Institutet, Stockholm, Sweden Abstract: NK cells are able to reject cells lacking expression of self MHC class I molecules. Inhibition of lysis is mediated by inhibitory receptors such as the murine Ly49. Two models have been proposed to account for the development of a useful Ly49 repertoire. We conducted mathematical modeling and computer simulation studies of each NK cell education model, fitting them to published and newly generated experimental data. Our results favor the two-step selection model over the sequential model, and raise several questions, which will be addressed in our future studies. Contact: shalmom1 [at] mail.biu.ac.il Keywords: Computer Simulations, Natural Killer Cells Poster L14 Structural Dynamics of the Cooperative Binding of the Human Cytochrome P450 (Cyp450) 3A4 Dan Fishelovitch (1), Haim J. Wolfson (2), Ruth Nussinov (1,3) (1) Sackler Institute of Molecular Medicine, Sackler Faculty of Medicine, Tel Aviv University, Israel; (2) School of Computer Science, Tel Aviv University, Israel; (3) IRSP - SAIC, Lab. of Experimental and Computational Biology, NCI - FCRDC, Frederick, MD, USA Abstract: Cytochrome P450 (Cyp450) 3A4 is a HEME containing enzyme that oxidizes 55% of swallowed drugs. The focus of this work is trying to understand the mechanism of cooperative binding (CB) in Cyp450 3A4. CB in this enzyme involves two substrates within the active site, which results in non Michaelis-Menten kinetics of the oxidation. The methods of this research involve Molecular Dynamics of the unbound enzyme, bound to one and to two substrates and doing comparative analysis of all runs. The mechanism of CB is unknown yet and the understanding of CB may aid in drug design. Contact: danfishl [at] post.tau.ac.il Keywords: CB Cooperative Binding, MD Molecular Dynamics Poster L15 Improving Cancer Therapy by Doxorubicin and GCSF: Insights from a Computerized Mathematical Model of Granulopoiesis Vladimir Vainstein (1), Yuval Ginosar (1), Meir Shoham (2), Anton Ianovski (2), Alexander Rabinovich (2), Yuri Kogan (1), Vera Selitser (1), Zvia Agur (1,2) (1) Institute for Medical Biomathematics; (2) Optimata Ltd. Abstract: Neutropenia is a significant dose-limiting toxicity of cancer chemotherapy. To identify more efficacious and less toxic treatment schedules, we studied a detailed physiologically-based computer model of granulopoiesis, as affected by doxorubicin and GCSF. We validated the model using clinical data on human granulopoiesis in healthy men and in cancer patients. We suggest improved doxorubicin regimens with lower myelotoxicity and higher dose intensity. These regimens are based on doxorubicin inter-dosing intervals being shortened to 9-10 days and on delayed administration of reduced GCSF doses. Contact: vladimir [at] imbm.org Keywords: GCSF, Granulopoiesis, Doxorubicin, Model Poster L17 A Gene Network Simulator Integrating Boolean Regulation in a Continuous Dynamic Model Barbara Di Camillo, Gianna Toffolo, Claudio Cobelli Information Engineering Department, University of Padova, Padova, Italy Abstract: Simulators of gene regulatory networks are needed to test and compare reverse engineering methods. We propose a new model to generate time series expression profiles from regulatory networks characterized by scale-free topology. The model integrates differential equation with Boolean logic so as to reproduce some important features of regulation in real biological systems. The model is able to generate synthetic time series data with characteristics similar to those of real experiments, which makes it suitable to test reverse engineering algorithms. Contact: dicamill [at] dei.unipd.it Keywords: Simulation, Reverse Engineering, Gene Network Poster L18 Analysis of Dynamics of Gene Regulatory Networks under Finite State Linear Model Dace Ruklisa (1), Alvis Brazma (2), Karlis Cerans (1), Juris Viksna (1) (1) IMCS, University of Latvia; (2) EBI, EMBL Abstract: We consider finite state linear models (FSLM) for describing gene regulatory networks. In this paper we look at the stability properties of FSLM networks. Usually slight changes in initial conditions do not shift behaviour of biological system radically. We try to capture these stability properties by providing tools for identification of stable regions and attractors within a network. Experiments with phage lambda networks showed that our methods can identify biologically meaningful attractors that correspond to characteristic phage lambda behaviours - lysis and lysogeny. Contact: dace.ruklisa [at] mii.lu.lv Keywords: Gene Regulatory Networks, Network Dynamics