De novo prediction of RNA 3D structures with deep generative models

PLoS One. 2024 Feb 15;19(2):e0297105. doi: 10.1371/journal.pone.0297105. eCollection 2024.

Abstract

We present a Deep Learning approach to predict 3D folding structures of RNAs from their nucleic acid sequence. Our approach combines an autoregressive Deep Generative Model, Monte Carlo Tree Search, and a score model to find and rank the most likely folding structures for a given RNA sequence. We show that RNA de novo structure prediction by deep learning is possible at atom resolution, despite the low number of experimentally measured structures that can be used for training. We confirm the predictive power of our approach by achieving competitive results in a retrospective evaluation of the RNA-Puzzles prediction challenges, without using structural contact information from multiple sequence alignments or additional data from chemical probing experiments. Blind predictions for recent RNA-Puzzle challenges under the name "Dfold" further support the competitive performance of our approach.

MeSH terms

  • Base Sequence
  • RNA* / chemistry
  • Retrospective Studies
  • Sequence Alignment

Substances

  • RNA

Grants and funding

JR and CB acknowledge funding from the Start-up Transfer.NRW (EFFRE-0400380, Nordrhein-Westfalen). CB MK and SH acknowledge funding from the Manchot Foundation, supporting interdisciplinary Artificial Intelligence research at the Heinrich Heine University. Both funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.