More than 40 Years Research on (Bio)Polymers DNA the ‚star‘ among the biomolecules and RNA the ‚magic molecule‘ Peter Schuster Institut für Theoretische Chemie, Universität Wien, Austria and The Santa Fe Institute, Santa Fe, New Mexico, USA Central European Symposium for Theoretical Chemistry 2009 Dobogók ő , 25.– 28.09.2009
Web-Page for further information: http://www.tbi.univie.ac.at/~pks
Born June 02, 1929 in Budapest Happy birthday Janos !
Cited by 440 articles
Cited by 55 articles
Cooperativity in intermolecular forces Cited by 42 articles
DNA, the ‚star‘ among the biomolecules
James D. Watson, 1928-, and Francis H.C. Crick, 1916-2004 Nobel prize 1962 1953 – 2003 fifty years double helix The three-dimensional structure of a short double helical stack of B-DNA
Modern phylogenetic tree: Lynn Margulis, Karlene V. Schwartz. Five Kingdoms . An Illustrated Guide to the Phyla of Life on Earth . W.H. Freeman, San Francisco, 1982.
The molecular clock of evolution Motoo Kimura. The Neutral Theory of Molecular Evolution . Cambridge University Press. Cambridge, UK, 1983.
Point mutation
Reconstruction of phylogenies through comparison of molecular sequence data
A model for the genome duplication in yeast 100 million years ago Manolis Kellis, Bruce W. Birren, and Eric S. Lander. Proof and evolutionary analysis of ancient genome duplication in the yeast Saccharomyces cerevisiae . Nature 428 : 617-624, 2004
A model for the genome duplication in yeast 100 million years ago Manolis Kellis, Bruce W. Birren, and Eric S. Lander. Proof and evolutionary analysis of ancient genome duplication in the yeast Saccharomyces cerevisiae . Nature 428 : 617-624, 2004
A model for the genome duplication in yeast 100 million years ago Manolis Kellis, Bruce W. Birren, and Eric S. Lander. Proof and evolutionary analysis of ancient genome duplication in the yeast Saccharomyces cerevisiae . Nature 428 : 617-624, 2004
A model for the genome duplication in yeast 100 million years ago Manolis Kellis, Bruce W. Birren, and Eric S. Lander. Proof and evolutionary analysis of ancient genome duplication in the yeast Saccharomyces cerevisiae . Nature 428 : 617-624, 2004
A sketch of a genetic and metabolic network
A B C D E F G H I J K L Biochemical Pathways 1 2 3 4 5 6 7 8 9 10 The reaction network of cellular metabolism published by Boehringer-Ingelheim.
The citric acid or Krebs cycle (enlarged from previous slide).
RNA, the ‚magic‘ biomolecule
RNA as scaffold for supramolecular complexes RNA as catalyst Ribozyme ribosome ? ? ? ? ? RNA RNA The world as a precursor of DNA protein the current + biology RNA as carrier of genetic information RNA viruses and retroviruses RNA evolution in vitro RNA – The magic molecule
N = 4 n N S < 3 n Criterion: Minimum free energy (mfe) Rules: _ ( _ ) _ � { AU , CG , GC , GU , UA , UG } A symbolic notation of RNA secondary structure that is equivalent to the conventional graphs
The notion of RNA (secondary) structure 1. Minimum free energy structure 2. Many sequences one structure 3. Suboptimal structures 4. Kinetic structures
The notion of RNA (secondary) structure 1. Minimum free energy structure 2. Many sequences one structure 3. Suboptimal structures 4. Kinetic structures
RNA sequence Biophysical chemistry: thermodynamics and kinetics RNA folding : Structural biology, spectroscopy of biomolecules, Vienna RNA-Package Empirical parameters understanding molecular function Version 1.8.3 http://www.tbi.univie.ac.at RNA structure of minimal free energy Sequence, structure, and design
Extension of the notion of structure
hairpin loop hairpin hairpin loop loop stack free stack stack joint stack end bulge free end free end stack internal loop stack hairpin loop Elements of RNA hairpin loop secondary structures multiloop hairpin as used in free energy loop calculations s t a c k stack stack ∑ ∑ ∑ ∑ ∆ = + + + + 300 free free ( ) ( ) ( ) L G g h n b n i n end 0 , end ij kl l b i stacks of hairpin bulges internal base pairs loops loops
J. Demez. European and mediterranean plant protection organization archive. France R.W. Hammond, R.A. Owens. Molecular Plant Pathology Laboratory, US Department of Agriculture Plant damage by viroids
Nucleotide sequence and secondary structure of the potato spindle tuber viroid RNA H.J.Gross, H. Domdey, C. Lossow, P Jank, M. Raba, H. Alberty, and H.L. Sänger. Nature 273 :203-208 (1978)
Vienna RNA Package 1.8.2 Biochemically supported structure Nucleotide sequence and secondary structure of the potato spindle tuber viroid RNA H.J.Gross, H. Domdey, C. Lossow, P Jank, M. Raba, H. Alberty, and H.L. Sänger. Nature 273 :203-208 (1978)
The notion of RNA (secondary) structure 1. Minimum free energy structure 2. Many sequences one structure 3. Suboptimal structures 4. Kinetic structures
RNA sequence Iterative determination of a sequence for the Inverse folding of RNA : given secondary RNA folding : structure Biotechnology, Structural biology, design of biomolecules spectroscopy of Inverse Folding with predefined biomolecules, Algorithm structures and functions understanding molecular function Vienna RNA-Package RNA structure Version 1.8.3 of minimal free energy http://www.tbi.univie.ac.at Sequence, structure, and design
Inverse folding algorithm I 0 � I 1 � I 2 � I 3 � I 4 � ... � I k � I k+1 � ... � I t S 0 � S 1 � S 2 � S 3 � S 4 � ... � S k � S k+1 � ... � S t I k+1 = M k (I k ) and � d S (S k ,S k+1 ) = d S (S k+1 ,S t ) - d S (S k ,S t ) < 0 M ... base or base pair mutation operator d S (S i ,S j ) ... distance between the two structures S i and S j ‚Unsuccessful trial‘ ... termination after n steps
Intermediate compatible sequences Initial trial sequences Stop sequence of an unsuccessful trial Intermediate compatible sequences Target sequence Target structure S k Approach to the target structure S k in the inverse folding algorithm
The inverse folding algorithm searches for sequences that form a given RNA secondary structure under the minimum free energy criterion.
I Space of genotypes: = { , , , , ... , } ; Hamming metric I I I I I 1 2 3 4 N S Space of phenotypes: = { , , , , ... , } ; metric (not required) S S S S S 1 2 3 4 M �� N M � ( ) = I S j k U � � -1 � � G k = ( ) | ( ) = I S I S k j j k � A mapping and its inversion
many genotypes � one phenotype
An example of ‘artificial selection’ with RNA molecules or ‘breeding’ of biomolecules
tobramycin RNA aptamer, n = 27 Formation of secondary structure of the tobramycin binding RNA aptamer with K D = 9 nM L. Jiang, A. K. Suri, R. Fiala, D. J. Patel, Saccharide-RNA recognition in an aminoglycoside antibiotic- RNA aptamer complex. Chemistry & Biology 4 :35-50 (1997)
The three-dimensional structure of the tobramycin aptamer complex L. Jiang, A. K. Suri, R. Fiala, D. J. Patel, Chemistry & Biology 4 :35-50 (1997)
RNA 9 :1456-1463, 2003 Evidence for neutral networks and shape space covering
Evidence for neutral networks and intersection of apatamer functions
The notion of RNA (secondary) structure 1. Minimum free energy structure 2. Many sequences one structure 3. Suboptimal structures 4. Kinetic structures
Extension of the notion of structure
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