RNAdualPF: software to compute the dual partition function with sample applications in molecular evolution theoryReport as inadecuate

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BMC Bioinformatics

, 17:424

Structural analysis


BackgroundRNA inverse folding is the problem of finding one or more sequences that fold into a user-specified target structure s0, i.e. whose minimum free energy secondary structure is identical to the target s0. Here we consider the ensemble of all RNA sequences that have low free energy with respect to a given target s0.

ResultsWe introduce the program RNAdualPF, which computes the dual partition functionZ, defined as the sum of Boltzmann factors exp−Ea,s 0-RT of all RNA nucleotide sequences a compatible with target structure s0. Using RNAdualPF, we efficiently sample RNA sequences that approximately fold into s0, where additionally the user can specify IUPAC sequence constraints at certain positions, and whether to include dangles energy terms for stacked, single-stranded nucleotides. Moreover, since we also compute the dual partition functionZk over all sequences having GC-content k, the user can require that all sampled sequences have a precise, specified GC-content.

Using Z, we compute the dual expected energy 〈E〉, and use it to show that natural RNAs from the Rfam 12.0 database have higher minimum free energy than expected, thus suggesting that functional RNAs are under evolutionary pressure to be only marginally thermodynamically stable.

We show that C. elegans precursor microRNA pre-miRNA is significantly non-robust with respect to mutations, by comparing the robustness of each wild type pre-miRNA sequence with 2000 resp. 500 sequences of the same GC-content generated by RNAdualPF, which approximately resp. exactly fold into the wild type target structure. We confirm and strengthen earlier findings that precursor microRNAs and bacterial small noncoding RNAs display plasticity, a measure of structural diversity.

ConclusionWe describe RNAdualPF, which rapidly computes the dual partition functionZ and samples sequences having low energy with respect to a target structure, allowing sequence constraints and specified GC-content. Using different inverse folding software, another group had earlier shown that pre-miRNA is mutationally robust, even controlling for compositional bias. Our opposite conclusion suggests a cautionary note that computationally based insights into molecular evolution may heavily depend on the software used.

C-C++-software for RNAdualPF is available at http:-bioinformatics.bc.edu-clotelab-RNAdualPF.

KeywordsRNA secondary structure Partition function Boltzmann ensemble Robustness AbbreviationsMFEMinimum free energy

PLMVdPeach latent mosaic viroid

sncRNASmall noncoding RNA

Electronic supplementary materialThe online version of this article doi:10.1186-s12859-016-1280-6 contains supplementary material, which is available to authorized users.

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Author: Juan Antonio Garcia-Martin - Amir H. Bayegan - Ivan Dotu - Peter Clote

Source: https://link.springer.com/

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