All-at-once RNA folding with 3D motif prediction framed by evolutionary information.

Structural RNAs exhibit a vast array of recurrent short 3D elements involving non-Watson-Crick interactions that help arrange canonical double helices into tertiary structures. We present CaCoFold-R3D, a probabilistic grammar that predicts these RNA 3D motifs (also termed modules) jointly with RNA secondary structure over a sequence or alignment. CaCoFold-R3D uses evolutionary information present in an RNA alignment to reliably identify canonical helices (including pseudoknots) by covariation.