Complete suboptimal folding of RNA and the stability of secondary structures

Stefan Wuchty, Walter Fontana, Ivo L. Hofacker, Peter Schuster

Research output: Contribution to journalReview articlepeer-review

421 Scopus citations


An algorithm is presented for generating rigorously all suboptimal secondary structures between the minimum free energy and an arbitrary upper limit. The algorithm is particularly fast in the vicinity of the minimum free energy. This enables the efficient approximation of statistical quantities, such as the partition function or measures for structural diversity. The density of states at low energies and its associated structures are crucial in assessing from a thermodynamic point of view how well-defined the ground state is. We demonstrate this by exploring the role of base modification in tRNA secondary structures, both at the level of individual sequences from Escherichia coli and by comparing artificially generated ensembles of modified and unmodified sequences with the same tRNA structure. The two major conclusions are that (1) base modification considerably sharpens the definition of the ground state structure by constraining energetically adjacent structures to be similar to the ground state, and (2) sequences whose ground state structure is thermodynamically well defined show a significant tendency to buffer single point mutations. This can have evolutionary implications, since selection pressure to improve the definition of ground states with biological function may result in increased neutrality.

Original languageEnglish (US)
Pages (from-to)145-165
Number of pages21
Issue number2
StatePublished - Feb 1999
Externally publishedYes


  • Density of states
  • Dynamic programming
  • Modified bases
  • Mutational buffering
  • Neutrality
  • RNA secondary structure
  • Suboptimal folding
  • Thermodynamic stability of structure
  • tRNA

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Biomaterials
  • Organic Chemistry


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