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DR CNRS
LIMSAG
University of Burgundy
Dijon (France)
Jean-Claude.Chambron@u-bourgogne.fr
http://www-chimie.u-strasbg.fr/~lcom/wppJCC.html
From Achirality and Euclidean Chirality
to Topological Chirality
Chirality means that object and mirror image are
not superimposable. This property of certain molecules is a central topic
of chemistry. Molecules are not just like any other objects : they can be
deformed, according to well established processes. This makes the concept
of chirality difficult to tackle without starting from achirality.
Euclidean chirality of a molecule results
from a well defined arrangement of its atoms in space, and therefore, from
some molecular rigidity. It is normally lost when the molecule is reduced
to its graph. This is not the case for topological chirality, which is
defined by the impossibility for the molecular object and its mirror image (called
enantiomers) to be transformed into each other by continuous deformation.
The existence of different degrees of topological chirality allows, starting
from Euclidean chirality, to establish a hierarchy of chirality, which will
be presented.
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Bioinformatic Professor
ESIL Biotechnology Engineering School
Mediterranean University
Marseille (France)
gautheret@esil.univ-mrs.fr
http://www.esil.univ-mrs.fr/~dgaut
RNA Motif Identification with the ERPIN
Program: Latest Improvements and Applications
ERPIN (Easy RNA Structure IdentificationN) is a new RNA motif search
program based on an adaptation of weight matrices, introducing
"secondary structure profiles" to deal with base paired regions.
ERPIN's input is an RNA sequence alignment where the common secondary
structure is annotated. From this alignment, we construct classical
lod-score profiles for single strands, and secondary structure profiles
with 16 lod-scores for each pair of correlated positions. An original
algorithm efficiently instanciate these profiles onto sequence
databases. Version 2 handles more complex motifs than the first
published version and implements multi stage searches in order to speed
up database scanning. I will present the algorithm of ERPIN 2 and new
biological results obtained with the program.
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CNRS, Biophysics and Soft condensed matter
LDFC,
Physics Institute
Louis Pasteur University
Strasbourg (France)
isambert
http://vivo.u-strasbg.fr/~isambert/
RNA Foldings and Unfoldings Kinetics
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Professor
Mathematics Dept - Physics and Astronomy Dept
University of Southern California
Los Angeles (USA)
rpenner@math.usc.edu
http://math.usc.edu/people/Penner/
Combinatorics of RNA Secondary
Structures
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LIFL UPRESA 8022 CNRS
Laboratoire d'Informatique Fondamentale de Lille |
Université des Sciences et Technologies de
Lille
Bâtiment M3
59655 Villeneuve D'Ascq Cedex
France
http://www.lifl.fr/~perrique
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Finding the common structure shared by
two
homologous RNAs
CARNAC (Computer Alignment of RNA by Cofolding) is a new method for
pairwise folding of RNA sequences. The program takes as input two
unaligned sequences in FASTA format, and produces a secondary structure in
CONNECT format. It proceeds in four steps: on one hand, it scans each
sequence for the best candidate stems; on the other hand, it searches for
the regions of high similarity between the two sequences, called 'anchor
points'; then, it performs a pairwise selection of stems, using
information furnished by anchor points and covariations; finally, it
constructs the common folding by energy minimization from the set of
pre-selected stems.
CARNAC can handle all RNA types, large well conserved sequences (16S ssu
rRNA), as well as poorly conserved RNAs (RNase P). It has also been
adapted to align a new homologous sequence along a reference structured
sequence.
Using different data sets, we compared our predictions with the commonly
accepted structure, which has been found by covariation method using a
large set
of aligned homologous sequences. We show that CARNAC provides a good
partial prediction with only two sequences. In presence of a whole family
of sequences, we also show that CARNAC can be used to detect if the
sequences are actually structured (mRNA, enteroviruses).
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Professor
Laboratory of Organo-mineral Chemistry
Le Bel institute - Louis Pasteur University
Strasbourg (France)
sauvage@chimie.u-strasbg.fr
http://wwwchimie.u-strasbg.fr/~lcom/
From Catenanes and Knots to Molecular
Devices
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Professor
Institute for Theoretical Chemistry and Molecular Structural Biology
Vienna University
Vienna (Austria)
pks@tbi.univie.ac.at
http://www.tbi.univie.ac.at/~pks/
Prediction and Analysis of RNA Secondary Structures
The
concept of RNA structure is discussed according to the physical conditions
applied. In particular, we consider: (1) secondary structures with minimum
free energy, (2) partition functions, and (3) kinetic folding of RNA.
Special emphasis is laid to the role of suboptimal conformations for the
properties of RNA molecules. Design of RNA molecules with predefined
structures and stabilities is realized by means of inverse folding – the
technique to find sequences for given structures – and a special design
algorithm. Kinetic folding may lead to sequences with multiple (meta)stable
states, so called switches, which are molecules that can switch between two
or more conformations and therefore may exhibit multiple properties. We
discuss one particular example of a sequence that forms two ribozymes with
two completely different catalytic properties. Finally we mention methods of
RNA structure determination, which are based on simultaneous alignments of
phylogenetically related sequences and structures.
Evolution in vitro and
Evolutionary Biotechnology
Adaptation through variation and
selection is the fundamental process in evolutionary optimization.
Biological evolution of higher organisms is an exceedingly complex
phenomenon and, moreover, it takes place on time scales, which are
prohibitive for experiments. Reduction of evolution in ecosystem to mutation
and selection in replicating ensembles of bacteria or RNA molecules under
controlled laboratory conditions solves both problems: (i) In the latter
case the system is simplified such that genotype-phenotype relations boil
down to relations between RNA sequences and RNA structures, which can be
interpreted with the current knowledge of structural biology, and (ii)
generation times are shortened tremendously, since bacteria multiply in less
than half an hour under optimal conditions, and RNA molecules replicate in a
few minutes or sometimes even faster. Consequently, adaptations to changes
in environmental conditions can be observed in a few days or, perhaps, in a
week. Optimization techniques, which are based on variation and selection,
have been applied successfully to the preparation of RNA and protein
molecules for predefined purposes. We present a brief introduction to the
principles of evolutionary design and discuss several successful examples.
Neutral Networks of RNA molecules and
RNA Evolution in silico
The RNA
model, in essence, is an in silico implementation of RNA evolution
and the underlying genotype-phenotype map is represented by a mapping from
RNA sequence space onto a space of so-called secondary structures, which are
simplified and coarse grained spatial structures of RNA molecules. This
sequence-to-structure map is highly redundant leaving ample room for
selective neutrality in the sense that many different sequences give rise to
the same secondary structure. The RNA model is sufficiently simple to allow
for mathematical analysis of the generic features of genotype-phenotype
mappings and, at the same time, it is sufficiently complex to reflect the
phenomena observed in real RNA evolution experiments. In particular, the
genotype-phenotype map based on RNA structures provides a straightforward
interpretation for a constructive role of neutral mutations in evolution.
The RNA model will be described and generalized to explore the generic
relations between genotypes and phenotypes. It will be used to analyze
adaptation to given environmental conditions and we shall present a concept
that allows for a formal distinction between minor or quasi-continuous
transitions and major improvements or innovations in optimization processes.
Finally, the results of a few recent experiments with RNA molecules will be
discussed in the light of the new concept of the interplay of neutral and
adaptive evolution.
References:
Peter Schuster.
Evolution in silico and in vitro. The RNA model. Biol.Chem.
382:1301-1314 (2001)
Christina Witwer,
Susanne Rauscher, Ivo. L. Hofacker, and Peter F. Stadler. Conserved RNA
secondary structures in picornaviridae genomes. Nucleic Acids Res.
29: 5079-5089 (2001)
Christoph Flamm,
Walter Fontana, Ivo L. Hofacker, and Peter Schuster. Elementary step
dynamics of RNA folding. RNA 6:325-338 (2000)
Stefan Wuchty, Walter
Fontana, Ivo L. Hofacker, and Peter Schuster.
Complete suboptimal folding of RNA and the stability of secondary
structures. Biopolymers 49:145-165 (1999)
Peter Schuster and
Walter Fontana. Chance and necessitiy in
evolution. Lessons from RNA. Physica D 133:427-452 (1999)
Walter Fontana and
Peter Schuster. Continuity in evolution. On the nature of transitions.
Science 280:1451-1455 (1998)
Christian Reidys,
Peter F. Stadler, and Peter Schuster. Generic properties of combinatory
maps. Neutral networks of RNA secondary structures. Bull.Math.Biol.
59:339-397 (1997)
Peter Schuster,
Walter Fontana, Peter F. Stadler, and Ivo L. Hofacker.
From sequences to shapes and back. A case study in RNA
secondary structures. Proc.Roy.Soc.London B 255:279-284
(1994).
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Professor
Laboratoire d'Analyse Ultrastructurale
Université de Lausanne
Switzerland
Construction and electrophoretic
migration of single-stranded DNA knots and catenanes.
In recent years there is a growing interest in the
question of how a particular topology of polymeric chains affects their
overall dimensions and physical behaviour. The majority of relevant studies
are based on numerical simulation methods or analytical treatment, however
both these approaches depend on various assumptions and simplifications.
Experimental verification is clearly needed but was hampered by practical
difficulty in obtaining preparative amounts of knotted or catenated polymers
with predefined topology and precisely set chain length. We introduce here
an efficient method of production of various single-stranded DNA knots and
catenanes that have the same global chain length. We also analyse
electrophoretic migration of such single-stranded DNA knots and catenanes
with increasing complexity.
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Professor
LAMI
Evry University
Evry (France)
tahi@lami.univ-evry.fr
DCFold,
an algorithm for RNA seconday structure
prediction
RNA secondary structures are particularly interesting structures.
Many important RNA molecules contain pseudoknots, which are generally
excluded by the definition of the secondary structure, mainly for
computational reasons. Most of proposed algorithms for the prediction of
the
secondary structure are not satisfactory in results and complexities,
even when pseudoknots are not allowed.
We present a fast algorithm, DCFold, that automatically predicts
the common secondary structure of a set of aligned homologous RNA
sequences. It is based on the comparative approach. Our algorithm
searches for palindromes that have a high probability to define helices
that are conserved
in the aligned sequences. This selection of significant palindromes is
based on criteria that take into account their length and their
mutation rate. A recursive search of helices is implemented using the ``divide
and conquer'' approach.
Indeed, a selected palindrome makes possible to divide the initial
sequence into two sequences, the internal one and the one resulting from
the concatenation of the two external ones. New palindromes can be
searched independently in these subsequences. In this step, pseudoknots
are not searched. An extension of DCFold, namely P-DCFold, had allowed to
detect also the pseudoknots, without increase the complexity.
The algorithm was run on several RNA sequences (rRNA 16S and 23S, tRNA,
tmRNA, RNaseP) and recovered very efficiently their secondary structures.
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