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Titel:
RNA in silico:
The Computational Biology of RNA Secondary Structures
Author(s):
Christoph Flamm,
Ivo L. Hofacker,
Peter F. Stadler
Appeared in:
Adv. Complex Systems, 2, 65-90 (1999)
Abstract:
RNA secondary structures provide a unique computer model for investigating
the most important aspects of structural and evolutionary biology. The
existence of efficient algorithms for solving the folding problem, i.e.,
for predicting the secondary structure given only the sequence, allows the
construction of realistic computer simulations. The notion of a
"landscape" underlies both the structure formation (folding) and the
(in vitro) evolution of RNA.
Evolutionary adaptation may be seen as hill climbing process on a
fitness landscape which is determined by the phenotype of the RNA
molecule (within the model this is its secondary structure) and the
selection constraints acting on the molecules. We find that a
substantial fraction of point mutations do not change an RNA secondary
structure. On the other hand, a comparable fraction of mutations leads
to very different structures. This interplay of smoothness and
ruggedness (or robustness and sensitivity) is a generic feature of
both RNA and protein sequence-structure maps. Its consequences,
"shape space covering" and "neutral networks" are inherited by the
fitness landscapes and determine the dynamics of RNA
evolution. Punctuated equilibria at phenotype level and a diffusion
like evolution of the underlying genotypes are a characteristic
feature of such models. As a practical application of these
theoretical findings we have designed an algorithm that finds
conserved (and therefore potentially functional) substructures of RNA
virus genomes from sparse data sets.
The folding dynamics of particular RNA molecule can also be studied
successfully based on secondary structures. Given an RNA sequence, we
consider the energy landscape formed by all possible conformations
(secondary structures). A straight forward implementation of the
Metropolis algorithm is sufficient to produce a quite realistic
folding kinetics, allowing to identify meta-stable states and folding
pathways. Just as in the protein case there are good and bad folders
which can be distinguished by the properties of their energy landscapes.
Keywords:
RNA Secondary Structures,
Fitness Landscapes,
Energy Landscapes,
Molecular Evolution,
Punctuated Equilibria,
Folding Kinetics,
Folding Pathways.
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