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Complete suboptimal folding of RNA and the stability of secondary structures
Author(s) -
Wuchty Stefan,
Fontana Walter,
Hofacker Ivo L.,
Schuster Peter
Publication year - 1999
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/(sici)1097-0282(199902)49:2<145::aid-bip4>3.0.co;2-g
Subject(s) - ground state , partition function (quantum field theory) , chemistry , statistical physics , nucleic acid secondary structure , stability (learning theory) , folding (dsp implementation) , base (topology) , base pair , function (biology) , partition (number theory) , physics , rna , quantum mechanics , combinatorics , mathematics , computer science , evolutionary biology , dna , mathematical analysis , biochemistry , machine learning , biology , electrical engineering , gene , engineering
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. © 1999 John Wiley & Sons, Inc. Biopoly 49: 145–165, 1999