Atomic accuracy in predicting and designing noncanonical RNA structure

A Rosetta full-atom framework, called fragment assembly of RNA with full-atom refinement (FARFAR), allows the de novo structure prediction and design of noncanonical RNA motifs with near-atomic resolution. We present fragment assembly of RNA with full-atom refinement (FARFAR), a Rosetta framework for predicting and designing noncanonical motifs that define RNA tertiary structure. In a test set of thirty-two 6–20-nucleotide motifs, FARFAR recapitulated 50% of the experimental structures at near-atomic accuracy. Sequence redesign calculations recovered native bases at 65% of residues engaged in noncanonical interactions, and we experimentally validated mutations predicted to stabilize a signal recognition particle domain.