Direct-Coupling Analysis of nucleotide coevolution facilitates RNA secondary and tertiary structure prediction
Abstract
Despite the biological importance of non-coding RNA, their structural characterization remains challenging. Making use of the rapidly growing sequence databases, we analyze nucleotide coevolution across homologous sequences via Direct-Coupling Analysis to detect nucleotide-nucleotide contacts. For a representative set of riboswitches, we show that the results of Direct-Coupling Analysis in combination with a generalized Nussinov algorithm systematically improve the results of RNA secondary structure prediction beyond traditional covariance approaches based on mutual information. Even more importantly, we show that the results of Direct-Coupling Analysis are enriched in tertiary structure contacts. By integrating these predictions into molecular model-ing tools, systematically improved tertiary structure predictions can be obtained, as compared to using secondary structure information alone.
Domains
Bioinformatics [q-bio.QM]
Origin : Publication funded by an institution
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