Theoretical Biochemistry Group

Institute for Theoretical Chemistry

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What we do and how we do it

We are working on a wide spectrum of problems mainly connected to theoretical chemistry, bioinformatics, and physics with impact and applications in all life sciences. The main directions are RNA computational biology, folding dynamics of molecules, RNA design and chemical reaction networks. In these fields we are developing and applying efficient methods to solve the associated problems.

RNA Computational Biology

RNA structures The development of algorithms to detect RNA genes, the prediction of their structure on different levels of abstraction, as well as the detailed characterization of these molecules form an essential topic in our research group.
Structured RNA elements are the building blocks of not only noncoding RNAs, such as tRNAs, miRNAs of spliceosomal RNAs, but form regulatory sub units of protein coding mRNAs as well, e.g. the terminator/anti-terminator system in bacteria. The methods and algorithms developed in our group use thermodynamic parameters to predict such RNA structures. In combination with expression data, e.g. taken from next generation sequencing (NGS) experiments, gene annotations, and sequence conservation information we predict, describe and functionally categorize ncRNA genes and regulatory RNA elements.
The Vienna RNA Package is a comprehensive collection of our computational methods, which comprises 22 programs plus 10 scripts for post processing of results.

Software

Webservices and Links

Selected Publications

Fast Folding and Comparison of RNA Secondary Structures
Ivo L. Hofacker, Walter Fontana, Peter F. Stadler, Sebastian Bonhoeffer, Manfred Tacker, Peter Schuster
In: Monatshefte Chemie, 1994, 125, 167-188
doi:10.1007/BF00818163 bibtex
ViennaRNA Package 2.0
Ronny Lorenz, Stephan H Bernhart, Christian Höner zu Siederdissen, Hakim Tafer, Christoph Flamm, Peter F. Stadler, Ivo L. Hofacker
In: Algorithms Mol Biol., 2011, 6, 26
doi:10.1186/1748-7188-6-26 bibtex
Identification and Analysis of Functional Elements in 1% of the Human Genome by the ENCODE Pilot Project
The ENCODE Consortium
Nature, 447: 799-816, 2007.
doi:10.1038/nature05874
Mapping of Conserved RNA Secondary Structures Predicts Thousands of Functional Noncoding RNAs in the Human Genome
Stefan Washietl, Ivo L. Hofacker, Melanie Lukasser, Alexander Hüttenhofer and Peter F. Stadler
Nat.Biotech., 23: 1383-1390, 2005.
doi:10.1038/nbt1144
Molecular evolution of a microRNA cluster
A Tanzer, PF Stadler
Journal of molecular biology 339 (2), 327-335, 2004
doi:10.1016/j.jmb.2004.03.065

Energy Landscapes and Folding Dynamics

Energy landscape Strongly connected to RNA computational biology studies is the investigation of RNA folding behaviors and dynamics. The application and development of methods to study such processes in terms of the underlying energy landscapes is a challenging but successful part of our research.
This is all-important for short-living molecules not reaching their thermodynamic equilibrium or for synthesis-guided structure formation during co-transcriptional folding. Our generic approaches are applied to study the dynamics of RNA or protein folding as well as physical models.

Software

Webservices and Links

Selected Publications

RNA Folding at Elementary Step Resolution
Christoph Flamm, Walter Fontana, Ivo L. Hofacker, Peter Schuster
In RNA, 2000, 6, 325-338
doi:10.1017/S1355838200992161 bibtex
Barrier Trees of Degenerate Landscapes
Christoph Flamm, Ivo L Hofacker, Peter F Stadler, Michael T Wolfinger
In Zeitschrift für Physikalische Chemie, 2002, 216, 2, 155
doi:10.1524/zpch.2002.216.2.155 bibtex
Efficient computation of RNA folding dynamics
Michael T Wolfinger, W Andreas Svrcek-Seiler, Christoph Flamm, Ivo L Hofacker, Peter F Stadler
In Journal of Physics A: Mathematical and General, 2004, 37, 17, 4731-4741
doi:10.1088/0305-4470/37/17/005 bibtex
BarMap: RNA folding on dynamic energy landscapes
Ivo L Hofacker, Christoph Flamm, Christian Heine, Michael T Wolfinger, Gerik Scheuermann, Peter F Stadler
In: RNA, 2010, 16, 7, 1308-1316
doi:10.1261/rna.2093310 bibtex
Basin Hopping Graph: A computational framework to characterize RNA folding landscapes
Marcel Kucharík, Ivo L. Hofacker, Peter F. Stadler and Jing Qin
Bioinformatics 2014
doi:10.1093/bioinformatics/btu156 bibtex

RNA Design

RNA design The lessons learned from computational RNA biology and folding dynamics allow us to develop methods to specifically design small regulatory RNAs with a variety of functions, such as ribozymes or riboswitches.
In synthetic biology, small functional RNA molecules have been recognized as versatile regulators of transcription and translation. Inspired by the field of mechanical engineering, RNA molecules can be used as small entities implementing regulation via logical gates.
We develop algorithms for the conformational design of RNAs and implement software for in silico prediction of new functional RNA molecules. Thereby, we focus on single functional self-interacting RNA devices, as well as networks of trans-acting RNAs.

Software

Webservices and Links

Selected Publications

Design of Multi-Stable RNA Molecules
Christoph Flamm, Ivo L. Hofacker, Sebastian Maurer-Stroh, Peter F. Stadler and Martin Zehl
RNA, 7, 254-265 (2001)
Publishers page
Computational Design of RNAs with Complex Energy Landscapes.
Christian Höner zu Siederdissen, Stefan Hammer, Ingrid Abfalter, Ivo L. Hofacker, Christoph Flamm, and Peter F. Stadler.
Biopolymers, 2013, 99, no. 12. 99: 1124–36.
doi:10.1002/bip.22337
De novo design of a synthetic riboswitch that regulates transcription termination
Manja Wachsmuth, Sven Findeiß, Nadine Weissheimer, Peter F Stadler and Mario Mörl
Nucleic Acids Research, 2012
doi:10.1093/nar/gks1330
Computational design of a circular RNA with prion-like behaviour
Stefan Badelt, Christoph Flamm and Ivo L. Hofacker
ALIFE 14 Confrence Proceedings (acepted)
Preprint

Chemical Reaction Networks

Chemical reaction network Modeling chemical reaction networks allows us to analyze all possible reactions within a system and their interconnection via different substrates. We developed an efficient graph grammar approach to describe these changes in connectivity within such networks over time while cascades of chemical reactions take place. Using such a formalism permits abstract reasoning about chemical reaction networks and allows us to identify reaction mechanisms underlying complex phenomena. We apply our methodology to a broad set of (bio)chemical problems such as synthesis planning or the evolution of catalyzed reaction networks.

Software

Selected Publications

Inferring chemical reaction patterns using rule composition in graph grammars
Jakob L Andersen, Christoph Flamm, Daniel Merkle, Peter F Stadler
J Sys Chem 4:4 (2013), doi:10.1186/1759-2208-4-4
A graph-based toy model of chemistry
Gil Benkö, Christoph Flamm, Peter F Stadler
In Journal of Chemical Information and Computer Sciences, 2003, 43, 4, 1085-1093
doi:10.1021/ci0200570 bibtex
Evolution of metabolic networks: a computational framework
Christoph Flamm, Alexander Ullrich, Heinz Ekker, Martin Mann, Daniel Högerl, Markus Rohrschneider, Sebastian Sauer, Gerik Scheuermann, Konstantin Klemm, Ivo L Hofacker, Peter F Stadler
In Journal of Systems Chemistry, 2010, 1, 1, 1-14
doi:10.1186/1759-2208-1-4 bibtex
The SBML ODE Solver Library: a native API for symbolic and fast numerical analysis of reaction networks
Rainer Machné, Andrew Finney, Stefan Müller, James Lu, Stefanie Widder, Christoph Flamm
In Bioinformatics, 2006, 22, 11, 1406-1407
doi:10.1093/bioinformatics/btl086 bibtex

Grants and Funding

Our research has been further backed by the following grants and funds.
(This is a comprehensive list starting from 2009).

  • Hofacker Ivo, Non-conding RNAs as ribo-regulators of gene expression and their role in disease
    GENAU II ncRNA, Feb 1, 2006 to Sep 30, 2009
  • Hofacker Ivo, Non-conding RNAs, from identification to functional characterization
    GENAU III ncRNA, Mar 1, 2009 to Feb 29, 2012
  • Hofacker Ivo, Bioingormatics-Integration Network II
    BIN II, Dec 1, 2005 to Nov 30, 2008
  • Hofacker Ivo, Bioinformatics-Integration-Network III
    BIN III, Jan 1, 2009 to Dec 31, 2011
  • Hofacker Ivo, In silico annotation of noncoding RNAs and their targets
    SFB F 4305-B09
  • Hofacker Ivo, Control of RNA function by conformational design
    I670-B11
  • Flamm Christoph, Redox Oscillation & Hormone feedback cycles
    MA04-005, 01.03.2008 - 01.03.2010
  • Flamm Christoph, Inverse Methods in Biology and Chemistry
    MA07-030, 01.06.2005 - 01.12.2008
  • Findeiss Sven, RiboNets
    Web Site, 01.09.2013 - 31.08.2016
  • Schuster Peter, Emergent organisation in complex biomolecular systems
    EMBIO 012835, 01.05.2005 - 01.05.2008
  • Stocsits Claudia, Ursprung des Adaptiven Immunsystems
    T369-B12
  • Thurner, Caroline, Genome dynamics
    P19411, 01.12.2006 - 30.11.2010