Neue konzeptionelle Ansätze zur Modellierung und Simulation komplexer Systeme / New Conceptual Approaches to Modeling and Simulation of Complex Systems

Bewilligungen / Grants 2004

Modelling large protein assemblies: from molecular machines to adhesion clusters

Bewilligung: 21.12.2004 Laufzeit: 3 Jahre

The proposed work combines methods from molecular simulations and statistical physics for the modelling of the dynamic assembly and disassembly of large supra-molecular complexes in biological systems. Identification of such complexes has recently become a central issue of proteomics research. Hereby, various processes occur on a multitude of time-scales from nanoseconds (formation of individual protein-protein complexes) to seconds (formation of entire supra-molecular complexes). While standard molecular simulation techniques are not capable of bridging these vastly different time scales, the authors propose to use the concept of an 'encounter complex'. In order to test the new methods, the well-defined problem of the assembly of the photosynthetic unit from reaction centers and light-harvesting complexes, and the functioning of focal adhesion are studied.

Universität Heidelberg
Interdisziplinäres Zentrum für
Wissenschaftliches Rechnen
Dr. Ulrich S. Schwarz
Im Neuenheimer Feld 368
69120 Heidelberg
Tel.: 06221 54 4986
Fax: 06221 54 5224

Universität des Saarlandes
Zentrum für Bioinformatik
Prof. Dr. Volkhard Helms
Geb. 17.1
66041 Saarbrücken
Tel.: 0681 302 64165
Fax: 0681 302 64180

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Rate theory for driven complex biosystems: stochastic modelling and computer simulations

Bewilligung: 06.12.2004 Laufzeit: 3 Jahre

This project deals with new concepts for modeling and simulation of two cross-disciplinary aspects of complex rate dynamics. The main objective is the study of rate-dominated processes as they occur for firing in single or ensembles of excitable neurons and for translocation of biomolecules (such as DNA, polymers, charged molecules, ions) through and towards nanopores, nanotubes and ion-channels. These systems are typically driven by explicitly time-dependent, noise-activated nonlinear escape events. A characteristic feature for all those complex processes is the presence of multiple time-scales. The work is focussed on the role of intrinsically or externally provided time-dependent forcing (via voltages or electric fields). This non-stationary manipulation promises the control of driven escape dynamics, and the characterization of crucial transport quantifiers.

Universität Augsburg
Institut für Physik
Lehrstuhl für Theoretische Physik I
Prof. Dr. Peter Hänggi
Universitätsstraße 1
86135 Augsburg
Tel.: 0821 598 3249/3250
Fax: 0821 598 3222

Humboldt-Universität Berlin
Institut für Physik
Prof. Dr. Lutz Schimansky-Geier
Newtonstraße 15
12489 Berlin
Tel.: 030 2093 7624
Fax: 030 2093 7638

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Novel simulation methods for electro-hydrodynamics

Bewilligung: 06.12.2004 Laufzeit: 3 Jahre

The authors plan to develop new efficient simulation methods for studying the dynamics of charged macromolecules in salt solutions, taking full account of the electrostatic and the hydrodynamic interactions in a variety of new ways. The newly developed methods for computing the electrostatic interactions should be able to handle the problem of a locally varying dielectric constant as it happens for example for the dielectric contrast between a wall and the solvent. The different methods will be compared to each other with respect to their accuracy and speed by applying them to simple problems like electroosmosis near a planar wall and by studying the electrophoretic motion of semi-flexible polyelectrolytes (such as DNA) confined in thin films of variable thickness. The team attempts to quantify the conditions under which hydrodynamic interactions and image charge effects play a significant role.

Universität Bielefeld
Fakultät für Physik
Theoretische Physik
Prof. Dr. Friederike Schmid
Postfach 10 01 31
33501 Bielefeld
Tel.: 0521 106 6191
Fax: 0521 106 6455

Max-Planck-Institut für Polymerforschung
Priv.-Doz. Dr. Burkhard Dünweg
Ackermannweg 10
D 55128 Mainz
Tel.: 06131 379 198 
Fax: 06131 379 100

Universität Frankfurt am Main
Frankfurt Institute for Advanced Studies
Priv.-Doz. Dr. Christian Holm
Robert Mayer Str. 10
D 60054 Frankfurt
Tel.: 069 798 47505 
Fax: 069 798 28734

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Generalized dynamics beyond molecular dynamics: Theory and simulation of collective conformational motions of biological macromolecules

Bewilligung: 06.12.2004 Laufzeit: 3 Jahre

Molecular dynamics (MD) simulation is currently the best available computational method to describe the dynamics and function of biological macromolecules such as proteins at the atomic level. Standard MD simulation is, however, severely limited in the timescale and number of atoms. For simulating internal motions of proteins or nucleic acids further into biologically-relevant timescales a combination of so far unconnected methods is investigated for drastically reducing the number of degrees of freedom and for accurately propagating the dynamics on the active subspace thus determined. Slow, collective protein motions will be identified from standard MD using principal component analysis, and the dynamics along these modes interpreted and modelled using the Langevin and generalized Langevin equations.

Max-Planck-Institut für
biophysikalische Chemie
Abt. für theoretische und computergestützte
Biophysik
Priv.-Doz. Dr. Helmut Grubmüller
Am Fassberg 11
37077 Göttingen
Tel.: 0551 201 2301/2300
Fax: 0551 201 2302
Homepage: http://www.mpibpc.gwdg.de/abteilungen/070

Universität Heidelberg
Interdisziplinäres Zentrum für Wissenschaftliches Rechnen
Lehrstuhl für Biocomputing
Prof. Dr. Jeremy Smith
Im Neuenheimer Feld 368
69120 Heidelberg
Tel.: 06221 54 8857
Fax: 06221 54 8868

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Adaptive multiscale simulation: connecting the quantum to the mesoscopic level

Bewilligung: 06.12.2004 Laufzeit: 3 Jahre

Most complex organic synthetic and biological systems can be characterized as 'soft matter'. The most universal aspect of soft matter is that the energy density is by many orders of magnitude lower compared to conventional solid state systems. As a consequence fluctuations play a very important role and many different length and time scales are relevant. To understand the interplay of the contributions from different scales, which lead to specific system properties and functions, a unified view covering many scales must be taken. In the project first attempts are undertaken to bridge scales for supramolecular structures from the quantum mechanical up to the mesoscopic level. As the ultimate goal an adaptive scheme is proposed, which allows a dynamical adjustment of the (detailed local) level of description depending on system properties.

Universität Bochum
Lehrstuhl für Theoretische Chemie
Prof. Dr. Dominik Marx

Universität Bochum
Lehrstuhl für Theoretische Chemie
Dr. Nikos L. Doltsinis

Max-Planck-Institut für
Polymerforschung
Abt. Theorie der Polymere
Prof. Dr. Kurt Kremer

Max-Planck-Institut für Polymerforschung
Abt. Theorie und Polymere
Dr. Luigi Delle Site

Ansprechpartner:
Universität Bochum
Lehrstuhl für Theoretische Chemie
Prof. Dr. Dominik Marx
Postfach
44780 Bochum
Tel.: 0234 32 28083
Fax: 0234 32 14045

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Ab initio multi-reference QM/MM methods for biomolecular simulations

Bewilligung: 06.12.2004 Laufzeit: 3 Jahre

The aim is to develop combined quantum-mechanical (QM) and molecular-mechanical (MM) methods for biomolecular simulations, which incorporate multi-reference configuration interaction (MR-CI) and second-order perturbation (MR-MP2) treatments as QM component. These methods are expected to be more accurate and more reliable than existing standard QM/MM approaches, and applicable to complex and electronically demanding biomolecular systems which cannot be described properly by single-reference QM treatments (for example, open-shell metalloenzymes and electronically excited states in proteins). First, existing codes will be integrated into the software ChemShell and validated. In the second stage, the functionality of these codes will be extended to meet the needs of large-scale QM/MM calculations on biomolecules.

Max-Planck-Institut für Kohlenforschung
Prof. Dr. Walter Thiel
Kaiser-Wilhelm-Platz 1
45470 Mülheim an der Ruhr
Tel.: 0208 306 2150
Fax: 0208 306 2996
Homepage: http://www.mpi-muelheim.mpg.de

Universität Würzburg
Institut für Organische Chemie
Prof. Dr. Bernd Engels
Am Hubland
97074 Würzburg
Tel.: 09131 888 5394
Fax: 09131 888 4606

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Modeling chromatin fibers by Monte Carlo procedures and analytical descriptions

Bewilligung: 06.12.2004 Laufzeit: 3 Jahre

A model of the 30 nm diameter chromatin fiber is developed that describes its spatial organization and dynamic properties. The model uses the nucleosomes and linker DNA as building blocks (size about 10 nm) to construct long fiber fragments with 500 nucleosomes (length about 1 micrometer). The aim is to study also the higher order folding of the fiber. The work is based on Monte Carlo simulations that will be complemented with analytical description. The features of the models will be tested and developed against experimental data from scanning force microscopy and force spectroscopy experiments. Predictions will be made on how biological factors would have to interact with the chromatin fiber to exert their function. The results from the modeling and simulations are expected to be highly relevant for a better understanding of gene expression regulation, since it is closely related to chromatin fiber conformation.

Universität Heidelberg
Kirchhoff-Institut für Physik
Molekulare Biophysik (F15)
Priv.-Doz. Dr. Karsten Rippe
Im Neuenheimer Feld 227
69120 Heidelberg
Tel.: 06221 54 9270
Fax: 06221 54 9112
Homepage: http://www.kip.uni-heidelberg.de/AG_Rippe/index.html

Fachhochschule Stralsund
FB Elektrotechnik und Informatik
System Engineering und Informationsmanagement
Prof. Dr. Gero Wedemann
Zur Schwedenschanze 15
18435 Stralsund
Tel.: 03831 457051
Fax: 03831 456687

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Regulatory mechanisms in cellular fiber systems

Bewilligung: 06.12.2004 Laufzeit: 3 Jahre

The project focuses on computer simulations to study regulatory aspects of intra-cellular architecture. The organization of systems composed of microtubules, which are dynamic polymers that grow or shrink by addition or removal of tubulin monomers, and associated regulatory proteins are studied. Their coupling creates a very interesting loop: the microtubule positions determine the local concentration of regulatory proteins, which in turn will determine the future microtubule positions. The author proposes to develop novel models and algorithms to simulate these regulation mechanisms. A previously used method based on unbiased parameter exploration to identify how elements should be combined to produce a given organization will be improved using modular simulations and optimization techniques.

EMBL - Europäisches Laboratorium
für Molekularbiologie
Cell Biology and Biophysics Unit
Dr. Francois Nedelec
Meyerhofstraße 1
69117 Heidelberg
Tel.: 06221 387342
Fax: 06221 387512

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Improved replica-exchange molecular dynamics sampling of conformational sub-states and folding of nucleic acids

Bewilligung: 06.12.2004 Laufzeit: 3 Jahre

Nucleic acids are involved in a variety of biological processes. Often the function of RNA and its interaction with ligands is mediated by nonhelical structural motifs such as bulges, internal or hairpin loops. These conformational structures and their dynamics cannot be detected using standard molecular dynamics simulations since this method allows only the imitation of nanosecond processes. During this time frame not all relevant molecular states are found. Therefore, the project aims at developing a new typ of 'replica exchange'-method to improve the sampling of conformational substates. Contrary to usual 'replica exchange' - methods the temperature coordinate will be substituted with an energy functional. The author expects that this ansatz can avoid artefacts like strang dissociation at high simulation temperatures.

International University Bremen (IUB)
School of Engineering and Sciences
Prof. Dr. Martin Zacharias
Postfach 750 561
28725 Bremen
Tel.: 0421 200 3541
Fax: 0421 200 3249

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New algorithms in charged soft and biological matter

Bewilligung: 06.12.2004 Laufzeit: 3 Jahre

Many biologically relevant macromolecules carry ionizable side-groups and contain hydrophobic parts. Since the non-polar, hydrohobic elements typically have a very low dielectric constant compared to water, electrostatic (solvation) self-energies and charge-charge interactions have to be evaluated in dielectrically inhomogeneous media. Due to technical reasons, these effects are neglected in all current (bio-)molecular simulations using implicit solvent models. The authors propose applying a new family of electrostatic algorithms to study the conformational properties of charged soft and biological matter. The algorithms allow direct incorporation of arbitrary dielectric effects in a manner which is both easy to program and numerically efficient.

Max-Planck-Institut für Physik
komplexer Systeme
Priv.-Doz. Dr. Ralf Everaers
Nöthnitzerstraße 38
01187 Dresden
Tel.: 0351 871 1206
Fax: 0351 871 1299

Ecole Supérieure de Physique
et de Chimie Industrielles ESPCI - CNRS
Laboratoire de Physico-Chimie Theorique
Dr. Anthony Maggs
10 rue Vauquelin
F-75231 Paris Cedex 05
FRANKREICH
Tel.: +33 1 40 79 4732

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From basic concepts and methods on the structure and function of complex networks to modeling of concrete real world networks

Bewilligung: 06.12.2004 Laufzeit: 2 Jahre

The central general idea for the research program on random graphs and complex systems is to further develop specific areas of probability theory and statistical physics. Random graphs and complex networks appear everywhere in real life (WWW, internet, social networks, biochemical networks,etc.). However, rigorous results are rare compared to the overall development of the field. A major goal of this project is to provide a link between theoretical research and fields of applications. Based on statistical mechanics and probability theory a general formation principle for complex networks, based on direct interaction between the elementary objects is developed. A special emphasis is put on new stochastic models for two particular processes, a spreading processs (modeling the phenomenon of corruption spreading in a society) and a synchronization process (modeling opinion dynamics in a society) taking into account the underlying network topology.

Universität Bielefeld
Fakultät für Physik
Theoretische Physik
Professor Dr. Philippe Blanchard
Postfach 10 01 31
33501 Bielefeld
Tel.: 0521 106 6205
Fax: 0521 106 2961

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Simulation models for cell motility - coupling substrate adhesion and cytoplasm dynamics

Bewilligung: 06.12.2004 Laufzeit: 3 Jahre

The ubiquitous phenomenon of cell spreading and migration on an adhesive substrate is a challenging research topic in molecular and cellular biomechanics with relevant biomedical applications. During the last ten years new experimental techniques have been developed and applied, allowing to formulate specific hypotheses about essential biochemical ingredients and biophysical mechanisms that induce cell-substrate adhesion, cell shape deformation and subsequent translocation. Two of the essential components are the diverse family of integrins, trans-membrane proteins responsible for attachment and force transmission to the extra-cellular matrix, and the contractile network of actin filaments with associated cross-linking proteins, for cell shape formation, force generation and for sensing mechanical stress. Aim of this project is to develop and explore modelling and simulation techniques on various spatial and temporal scales, which are suited to couple the dynamics of these two molecular components.

Universität Bonn
Botanisches Institut und Botanischer Garten
Abt. Theoretische Biologie
Prof. Dr. Wolfgang Alt
Kirschallee 1
53115 Bonn
Tel.: 0228 73 5577
Fax: 0228 73 5513

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Stochastic modeling of the proteasome and its application in cancer therapy

Bewilligung: 26.11.2004 Laufzeit: 3 Jahre

This research project focuses on the application of principles of noise-induced phenomena to a complex molecular machine, the proteasome, and on the investigation of its activity control for medical purposes. The modeling methodology assumes a constructive role of fluctuations, provided by internal stochasticity or external influence. The aim is to develop a stochastic model of the proteasom and to shed light on the nature of directed transport of proteins in the proteasome and on mechanisms regulating the size of the proteasome products. This may lead to new concepts for the treatment of pathological effects and diseases, highly influenced by the proteasome. Calculations of fluctuationally and peptide size dependent transport rates are planned in order to explain the influence of fluctuations, e.g. temperature, on the organization of immune defense in humans or mammals as well as to suggest possible experimental set-ups and new strategies of medical treatment, especially in cancer therapy. Additionally, this research will contribute to a theoretical topic of current importance: the theory of spatially extended complex systems with noise.

Institut für Physik der Universität Potsdam 
Dr. Zaikin
Am Neuen Palais 10, Haus 19
14469 Potsdam
Tel.: 0331 977 1639
Fax: 0331 977 1142

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International Symposium "Windows to complexity"

04.04.2005 - 06.04.2005 in Münster

Universität Münster
Institut für Theoretische Physik
Professor Dr. Rudolf Friedrich
Wilhelm-Klemm-Straße 9
48149 Münster
Tel.: 0251 83 349100
Fax: 0251 83 36328
Homepage: http://pauli.uni-muenster.de/tp/menu/organisation/mitarbeiter.html

Universität Münster
Institut für Festkörpertheorie
Prof. Dr. Tilmann Kuhn
Wilhelm-Klemm-Str. 10
48149 Münster
Tel.: 0251 83 36312
Fax: 0251 83 33669

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Schriftgröße