Complete suboptimal folding of RNA and the stability of secondary structures

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

Research output: Contribution to journalArticle

396 Citations (Scopus)

Abstract

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
JournalBiopolymers
Volume49
Issue number2
DOIs
StatePublished - Feb 1999
Externally publishedYes

Fingerprint

RNA Stability
Transfer RNA
RNA
Ground state
Thermodynamics
Point Mutation
Buffers
Free energy
Escherichia coli
Pressure

Keywords

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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Biophysics

Cite this

Complete suboptimal folding of RNA and the stability of secondary structures. / Wuchty, Stefan; Fontana, Walter; Hofacker, Ivo L.; Schuster, Peter.

In: Biopolymers, Vol. 49, No. 2, 02.1999, p. 145-165.

Research output: Contribution to journalArticle

Wuchty, Stefan ; Fontana, Walter ; Hofacker, Ivo L. ; Schuster, Peter. / Complete suboptimal folding of RNA and the stability of secondary structures. In: Biopolymers. 1999 ; Vol. 49, No. 2. pp. 145-165.
@article{ce017634b9d243b793d80337335c846c,
title = "Complete suboptimal folding of RNA and the stability of secondary structures",
abstract = "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.",
keywords = "Density of states, Dynamic programming, Modified bases, Mutational buffering, Neutrality, RNA secondary structure, Suboptimal folding, Thermodynamic stability of structure, tRNA",
author = "Stefan Wuchty and Walter Fontana and Hofacker, {Ivo L.} and Peter Schuster",
year = "1999",
month = "2",
doi = "10.1002/(SICI)1097-0282(199902)49:2<145::AID-BIP4>3.0.CO;2-G",
language = "English (US)",
volume = "49",
pages = "145--165",
journal = "Biopolymers - Peptide Science Section",
issn = "0006-3525",
publisher = "John Wiley and Sons Inc.",
number = "2",

}

TY - JOUR

T1 - Complete suboptimal folding of RNA and the stability of secondary structures

AU - Wuchty, Stefan

AU - Fontana, Walter

AU - Hofacker, Ivo L.

AU - Schuster, Peter

PY - 1999/2

Y1 - 1999/2

N2 - 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.

AB - 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.

KW - Density of states

KW - Dynamic programming

KW - Modified bases

KW - Mutational buffering

KW - Neutrality

KW - RNA secondary structure

KW - Suboptimal folding

KW - Thermodynamic stability of structure

KW - tRNA

UR - http://www.scopus.com/inward/record.url?scp=0033080745&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033080745&partnerID=8YFLogxK

U2 - 10.1002/(SICI)1097-0282(199902)49:2<145::AID-BIP4>3.0.CO;2-G

DO - 10.1002/(SICI)1097-0282(199902)49:2<145::AID-BIP4>3.0.CO;2-G

M3 - Article

C2 - 10070264

AN - SCOPUS:0033080745

VL - 49

SP - 145

EP - 165

JO - Biopolymers - Peptide Science Section

JF - Biopolymers - Peptide Science Section

SN - 0006-3525

IS - 2

ER -