Dr. Gabriel Schaaf
Center for Plant Molecular Biology,ZMBP
Plantphysiology
Universtät Tübingen

Prof. Vytas A. Bankaitis
School of Medicine
Department of Cell & Developmental Biology
University of North Carolina at Chapel Hill

Marek Dynowski
Center for Plant Molecular Biology,ZMBP
Plantphysiology
Universtät Tübingen

Eva Winkelbauer
Center for Plant Molecular Biology,ZMBP
Plantphysiology
Universtät Tübingen

Marília Kaphan Freitas de Campos
Center for Plant Molecular Biology,ZMBP
Plantphysiology
Universtät Tübingen

Sec14p is the major phosphatidylinositol (PtdIns) / phosphatidylcholine (PtdCho) transfer protein (PITP) in the budding yeast Saccharomyces cerevisiae and is the founding member of the large eukaryotic PITP superfamily. PITPs are defined by their ability to transfer PtdIns and PtdCho between membrane bilayers in vitro in an energy independent fashion. In yeast, Sec14 is essential for the efficient biosynthesis of phosphoinositides (phosphorylated species of PtdIns) and thus vesicle formation at the trans-Golgi network. Deficiencies of Sec14-like proteins cause diseases in animals and humans and developmental defects in plants.

Recently solved high resolution structures of Sec14 homolog Sfh1 in complex with PtdIns and PtdCho revealed a hydrophobic pocket large enough to accommodate a single phospholipid molecule. Both physiological Sec14 subtrates, PtdIns and PtdCho, occupy overlapping, yet distinct, positions within this hydrophobic pocket. Functional studies indicate that: i) individual binding of both PtdIns and PtdCho represents essential activities of Sec14, ii) Sec14 likely presents PtdIns to a downstream PtdIns -4OH kinase during a phospholipid exchange reaction (PtdIns versus PtdCho), hereby overcoming an intrinsic inefficiency of lipid kinases to recognize their lipid substrate in the native membrane bilayer.

The mechanism of this exchange/presentation reaction is unknown and cannot be addressed by crystallographic studies in a straightforward way. To this end we have performed a directed evolution screen with Sec14 homolog Sfh1 which lacks essential Sec14 properties such as stimulation of phosphoinositide biosynthesis in vivo and growth complementation of Sec14 defects in yeast. We identified Sfh1 activation mutants (Sfh1*) that harbor single amino acid substitutions and endow Sfh1 with Sec14-like activities. However, the molecular mechanism that leads to Sec14-like activities of Sfh1* is not deducible from static crystal structures and homology models. To investigate the Sfh1* activation phenotype and to understand Sec14-mediated phospholipid exchange/presentation we will conduct extensive molecular dynamics simulations on crystal structures and homology models of Sfh1, Sec14 and the Sfh1 activation mutants.

• Schaaf G, Ortlund EA, Tyeryar KR, Mousley CJ, Ile KE, Garrett TA, Ren J, Woolls MJ, Raetz CR, Redinbo MR, Bankaitis VA: Functional anatomy of phospholipid binding and regulation of phosphoinositide homeostasis by proteins of the sec14 superfamily, Mol Cell. 29(2):191-206 (2008)
• Schaaf et al., in preperation

PD Dr. Uwe Ludewig
TU Darmstadt / FB Biologie / Plant Nutrition and Biomass
TU Darmstadt

Dr. Benjamin Neuhäuser
Institute for Molecular Infection Biology
Universität Würzburg

Marek Dynowski
Center for Plant Molecular Biology,ZMBP
Plantphysiology
Universtät Tübingen

Daniel Straub
TU Darmstadt / FB Biologie / Plant Nutrition and Biomass
TU Darmstadt

The ammonium flux across prokaryotic, plant and animal membranes is regulated by ammonium transporters (AMT) and/or the related Rhesus (glyco-)proteins. Rh proteins facilitate NH3 transport via selective, hydrophobic narrow pores. Electroneutral transport of uncharged NH3 is proposed for many prokaryotic members of the AMT family, although experiments suggest that they recruit NH4+ in a substrate binding site. It was suggested that NH4+ is deprotonated before uncharged NH3 is conducted. Despite a highly conserved pore structure in prokaryotic and plant AMTs, the homologs from plants apparently conduct NH4+, as an ionic current is elicited by ammonium when these are expressed in oocytes. The charge transport by plant AMTs contrasts the suggested mechanism of NH3 conduction by other AMTs. A combination of laboratory experiments and molecular dynamics simulations will be used to investigate the transport mechanism in electrogenic plant AMTs. Steered MD will be performed with a homology model of a plant AMT. NH3 or NH4+ will be tested as substrates. The simulated systems will consist of the trimeric protein embedded in a 1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylethanolamine (POPE, 16:0/18:1;9) bilayer membrane that is surrounded by explicit solvent. The pores of the AMTs are aligned along the z-axis and a constant force into z-direction is applied to the substrate molecules to push the molecule into the pore entrance. The force will be released subsequently and additional 5 ns of unconstrained dynamics will be performed. The substrate specificity and physio/chemical properties of the cation binding site should be identified and characterized. As a control, similar MD simulations will be performed with the crystal structure of the archaeal AfAMT-1. The crucial amino acids involved in the coordination and conduction of the substrate molecules will be determined and these amino acids will be mutated and directly assayed using transport assays. These mutants will also be characterized computationally, and homology models will be used for further extensive MD simulations, which will all be computed in the bwGRiD.

• Neuhäuser, Dynowski, Straub, Ludewig, in preperation
• Channel-like NH3 flux by ammonium transporter AtAMT2., Neuhäuser B, Dynowski M, Ludewig U., FEBS Lett. 583(17):2833-8. (2009)
• Molecular mechanisms of ammonium transport and accumulation in plants., Ludewig U, Neuhäuser B, Dynowski M., FEBS Lett. 581(12):2301-8. (2007)
• Regulation of NH4+ transport by essential cross talk between AMT monomers through the carboxyl tails., Neuhäuser B, Dynowski M, Mayer M, Ludewig U., Plant Physiol., 143(4):1651-9. (2007)

PD Dr. Uwe Ludewig
TU Darmstadt / FB Biologie / Plant Nutrition and Biomass
TU Darmstadt

Dr. Oscar Moran
Istituto di Biofisica
Consiglio Nazionale delle Ricerche

Dr. Maria Mayer
Center for Plant Molecular Biology,ZMBP
Plantphysiology
Universtät Tübingen

Dr. Gabriel Schaaf
Center for Plant Molecular Biology,ZMBP
Plantphysiology
Universtät Tübingen

Marek Dynowski
Center for Plant Molecular Biology,ZMBP
Plantphysiology
Universtät Tübingen

Transmembrane channels of the "major intrinsic protein" (MIP) family (also depicted as aquaporins and/or aquaglyceroporins) participate in the selective uptake and distribution of water in the plant. MIPs also regulate the permeability of plant membranes to small, uncharged nutrients or other molecules. Despite a high structural similarity, these channels show a surprisingly wide substrate spectrum. A combination of molecular dynamics and laboratory experiments will be used to investigate the molecular determinants of the substrate specificity in different MIPs. Steered molecular dynamics and homology modeling will be used to identify important amino acids involved in the substrate selection process. Monomoeric and a tetrameric structural models of the MIP channel PIP2;1 from Spinacia oleracea will be embedded in a 1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylethanolamine (POPE, 16:0/18:1;9) lipid bilayer. The channels are aligned along the z-axis and a constant force into z-direction will be applied to the substrate molecules. The conduction of potential substrates, such as water, ammonia or urea will be compared. Furthermore, the potential capability of MIP channels to conduct the important signaling compound H2O2 will be investigated. Crucial residues for the selectivity will be identified from the simulations, and their impact will be experimentally verified using transport assays, using AtPIP2;1 pore mutants. These extensive MD simulations will be computed in the bwGRiD.

• Dynowski M, Mayer M, Moran O, Ludewig U, Molecular determinants of ammonia and urea conductance in plant aquaporin homologs., FEBS Lett., 582(16):2458-62 (2008)
• Dynowski M, Schaaf G, Loque D, Moran O, Ludewig U, Plant plasma membrane water channels conduct the signalling molecule H2O2., Biochem J., 414(1):53-61 (2008)
• Ludewig U., Dynowski M., Plant aquaporin selectivity: where transport assays, computer simulations and physiology meet.Cell Mol Life Sci., 66(19):3161-75 (2009)

Burkhard Zink
Theoretische Astrophysik
Fachbereich Physik
Universtät Tübingen

Oleg Korobkin
Center for Computation and Technology
Louisiana State University

Erik Schnetter
Center for Computation and Technology
Louisiana State University

Nikolaos Stergioulas
Department of Physics, Section of Astrophysics, Astronomy and Mechanics
University of Thessaloniki

Rapidly rotating neutron stars can be unstable to the gravitational-wave-driven CFS mechanism if they have a neutral point in the spectrum of nonaxisymmetric f-modes. We investigate the frequencies of these modes in two sequences of uniformly rotating polytropes using nonlinear simulations in full general relativity, determine the approximate locations of the neutral points, and derive limits on the observable frequency band available to the instability in these sequences. We find that general relativity enhances the detectability of a CFS-unstable neutron star substantially, both by widening the instability window and enlarging the band into the optimal range for interferometric detectors like LIGO, VIRGO, and GEO-600.

• B. Zink, O. Korobkin, E. Schnetter, N. Stergioulas. Phys. Rev. D., in press.

Dr. Alexander Auch
Universität Tübingen

Sandra Gesing
Universität Tübingen

PD Dr. Markus Göker
Deutsche Sammlung von Mikroorganismen und Zellkulturen (DSMZ), Braunschweig

PD Dr. Hans-Peter Klenk
Deutsche Sammlung von Mikroorganismen und Zellkulturen (DSMZ), Braunschweig

According to the principle as stated by Dobzhansky, "nothing in biology makes sense except in the light of evolution",in this project we try to shed light into the evolutionary history of prokaryotic (comprising bacteria and archaea) species.The formidable increase in available computing power due to the promotion of Grid computing projectsopens up new perspectives in analysing large-scale phylogenetic relationships based on entire prokaryotic genomes.By using entire genomes instead of single genes, biases due to horizontally transferred genes or saturational effects canbe compensated for.Calculations of intergenomic distances and reconstruction of phylogenetic trees and networks mainly are conducted on the bwGRiD.

• Press release of the DSMZ (german): Verwandtschaft von Bakterien am Computer bestimmen, idw-online.de/pages/de/news360619
• Presentation given at the 3rd joint conference of the DGHM and the VAAM, ggdc.gbdp.org/docs/Goeker_VAAM_2010.pdf
• A.F. Auch, H.-P. Klenk, M. Göker: Standard operating procedure for calculating genome-to-genome distances based on high-scoring segment pairs. Standards in Genomic Sciences 2(1):142-148, 2010.
• A.F. Auch, M. Von Jan, H.-P. Klenk, M. Göker: Digital DNA-DNA hybridization for microbial species delineation by means of genome-to-genome sequence comparison. Standards in Genomic Sciences 2(1):117-134, 2010.
• A.F. Auch, S.R. Henz, M. Göker: Phylogenies from whole genomes - Methodological update within a distance-based framework. Poster at German conference on Bioinformatics, Tübingen 2006.
• A.F. Auch, S.R. Henz, B. Holland, M. Göker: Genome blast distance phylogenies inferred from whole plastid and whole mitochondrion genome sequences. BMC Bioinformatics 7: 350, 2006.
• S.R. Henz, D.H. Huson, A.F. Auch, K. Nieselt-Struwe, S.C. Schuster: Whole-genome prokaryotic phylogeny. Bioinformatics 21:2329-2335, 2005.

Michael Kaufmann
Wilhelm-Schickard-Institut für Informatik
Paralleles Rechnen
Universtät Tübingen

Wolfgang Küchlin
Wilhelm-Schickard-Institut für Informatik
Symbolisches Rechnen
Universtät Tübingen

Stephan Kottler
Wilhelm-Schickard-Institut für Informatik
Paralleles Rechnen
Universtät Tübingen

Given a boolean formula the satisfiability problem (SAT) asks if there exists a truth assignment to the variables of the formula such that the formula evaluates to true. Even though this problem seems to be purely theoretical there are several real-world problems that can be formulated as a SAT problem like hardware and software verification, planning, automotive product configuration and problems in bioinformatics. From the theoretical point of view SAT is NP-complete and should thus be not solvable in feasible time. However, in the last 15 years state-of-the-art SAT Solvers became able to tackle many real-world SAT instances with hundreds and thousands of variables. We aim to improve SAT solving by analysing and enhancing current solving techniques. Our main goal is to allow for more structural analysis of instances during the solving process. Moreover, we implement and evaluate hybrid and parallel solving techniques to combine different successful approaches to one robust solver. This work requires extensive evaluation and verification of the solver on huge sets of benchmarks. In the international SAT-competition 2009 our solver was able to win the silver medal in the category of satisfiable crafted instances.

• S. Kottler: SAT Solving with Reference Points, Theory and Applications of Satisfiability Testing (SAT 2010), 2010
• M. Kaufmann, S. Kottler: Proving or Disproving Planar Straight-Line Embeddability onto given Rectangles, 17th International Symposium on Graph Drawing (GD '09), 2010
• S. Kottler, M. Kaufmann, C. Sinz: Computation of Renameable Horn Backdoors, Theory and Applications of Satisfiability Testing (SAT 2008), 2008

Markus Flaig
Theoretische Astrophysik
Fachbereich Physik
Universitaet Tuebingen

Willy Kley
Theoretische Astrophysik
Fachbereich Physik
Universitaet Tuebingen

Patrick Ruoff
Theoretische Astrophysik
Fachbereich Physik
Universitaet Tuebingen

We study protoplanetary accretion discs that are turbulent due to the magnetorotational instability (MRI). The disc model consists of a rectangular box that is cut out of the disc. The disc gas is described by the equations of ideal magnetohydrodynamics (MHD). In order to achieve a self-consistent model, we include radiation transport. This allows us to track in detail the energy transport in protoplanetary discs: Energy from the Keplerian shear flow is converted into turbulent motions, these are then dissipated into heat at small scales, the heat is transported by radiative diffusion and finally radiated away into space. After a long journey, some of this radiation eventually reaches the earth and is detected by human observers. A long-term goal of our project is to derive constraints on disc models by matching the results from numerical protoplanetary disc models with actual observations. In order to achieve a truly self-consistent protoplanetary disc model, we have more recently started to include also chemistry into our model. Most of the simulations performed so far were done using the computational resources provided by the bwGRiD.

The picture shows a snapshot of the magnetic field strength from a high-resolution (64x128x512) MRI-turbulent radiative MHD simulation.

• M. Flaig, R. Kissmann and W. Kley, Linear Growth of the MRI – the Influence of Radiation Transport, MNRAS 394, 1887-1896 (2009)
• M. Flaig, W. Kley and R. Kissmann, Modeling Radiation Transport in MRI-turbulent Protoplanetary Discs, MNRAS, submitted

Anna Chizhik
Institut für Physikalische und Theoretische Chemie
Fakultät für Chemie und Pharmazie
Universtät Tübingen

Hans-Georg Mack
Institut für Physikalische und Theoretische Chemie
Fakultät für Chemie und Pharmazie
Universtät Tübingen

Alfred J. Meixner
Institut für Physikalische und Theoretische Chemie
Fakultät für Chemie und Pharmazie
Universtät Tübingen

Tautomerism of the single fluorescent molecules can be studied by means of confocal microscopy in combination with azimuthally or radially polarized laser beams. In a tautomerisation process the transition dipole moment of the molecule changes the direction and these changes can be visualized by the fluorescence excitation image of the molecule. The applicability of the method for the study of tautomerism is limited by the exact structure of the molecules. Comprehensive experimental and theoretical studies of various types of porphyrazines and prophyrins demonstrate that the angle between the transition dipole moments of the corresponding tautomers must lay in the range between 60 and 120 degree in order to distinguish the fluorescence patterns from that of a single dipole.

Extensive quantum chemical calculations supporting the experimental investigations and confirming their results are carried out in the bwGRiD.

• Marcus Sackrow, Anna Chizhik, Catrinel Stanciu, Sergej Vagin, Mrio J.F. Calvete, Hans-Georg Mack, Michael Hanack and Alfred J. Meixner, Single molecule tautomerism imaging of porphyrazines, J. Phys. Chem., submitted

Bertram Bitsch
Theoretische Astrophysik
Fachbereich Physik
Universtät Tübingen

Willy Kley
Theoretische Astrophysik
Fachbereich Physik
Universtät Tübingen

The migration of growing protoplanets depends on the thermodynamics of the ambient disc. Standard modelling, using locally isothermal discs, indicate an inward (type-I) migration in the low-mass planet regime. Taking non-isothermal effects (e.g. radiation) into account, recent studies have shown that the direction of the type-I migration can change from inward to outward. This effect is based upon the change of density near the planet due to the change in temperature. This torque reversal is important in the evolution of planets in a solar system. In the picture we display the surface density of a low mass planet in a fully radiative disc.

The extensive simulations and parameter studies to prove this thesis were computed in the bwGRiD.

• W. Kley, B. Bitsch, and H. Klahr, Planet migration in three-dimensional radiative discs, A&A 506, 971-987 (2009)
• B. Bitsch and W. Kley, in preperation