De NovoRNA Tertiary Structure Prediction at Atomic Resolution Using Geometric Potentials from Deep Learning

ABSTRACT Experimental characterization of RNA structure remains difficult, especially for non-coding RNAs that are critical to many cellular activities. We developed DeepFoldRNA to predict RNA structures from sequence alone by coupling deep self-attention neural networks with gradient-based folding simulations. The method was tested on two independent benchmark datasets from Rfam families and RNA-Puzzle experiments, where DeepFoldRNA constructed models with an average RMSD=2.69 Å and TM-score=0.743, which outperformed state-of-the-art methods and the best models submitted from the RNA-Puzzles community by a large margin. On average, DeepFoldRNA required ~1 minute to fold medium-sized RNAs, which was ~350-4000 times faster than the leading Monte Carlo simulation approaches. These results demonstrate the major advantage of advanced deep learning techniques to learn more accurate information from evolutionary profiles than knowledge-based potentials derived from simple statistics of the PDB library. The high speed and accuracy of the developed method should enable large-scale atomic-level RNA structure modeling applications.