Open AccessRNA structure prediction using positive and negative evolutionary information
Author(s) -
Elena Rivas
Publication year - 2020
Publication title -
plos computational biology/plos computational biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.628
H-Index - 182
eISSN - 1553-7358
pISSN - 1553-734X
DOI - 10.1371/journal.pcbi.1008387
Subject(s) - antiparallel (mathematics) , rna , nucleic acid structure , folding (dsp implementation) , conserved sequence , computational biology , nucleic acid secondary structure , biology , protein structure , evolutionary biology , genetics , computer science , base sequence , dna , gene , physics , quantum mechanics , magnetic field , electrical engineering , engineering , biochemistry
Knowing the structure of conserved structural RNAs is important to elucidate their function and mechanism of action. However, predicting a conserved RNA structure remains unreliable, even when using a combination of thermodynamic stability and evolutionary covariation information. Here we present a method to predict a conserved RNA structure that combines the following three features. First, it uses significant covariation due to RNA structure and removes spurious covariation due to phylogeny. Second, it uses negative evolutionary information: basepairs that have variation but no significant covariation are prevented from occurring. Lastly, it uses a battery of probabilistic folding algorithms that incorporate all positive covariation into one structure. The method, named CaCoFold (Cascade variation/covariation Constrained Folding algorithm), predicts a nested structure guided by a maximal subset of positive basepairs, and recursively incorporates all remaining positive basepairs into alternative helices. The alternative helices can be compatible with the nested structure such as pseudoknots, or overlapping such as competing structures, base triplets, or other 3D non-antiparallel interactions. We present evidence that CaCoFold predictions are consistent with structures modeled from crystallography.