Accurate RNA 3D structure prediction using a language model-based deep learning approach
Abstract
Accurate prediction of RNA three-dimensional (3D) structure remains an unsolved challenge. Determining RNA 3D structures is crucial for understanding their functions and informing RNA-targeting drug development and synthetic biology design. The structural flexibility of RNA, which leads to scarcity of experimentally determined data, complicates computational prediction efforts. Here, we present RhoFold+, an RNA language model-based deep learning method that accurately predicts 3D structures of single-chain RNAs from sequences. By integrating an RNA language model pre-trained on ~23.7 million RNA sequences and leveraging techniques to address data scarcity, RhoFold+ offers a fully automated end-to-end pipeline for RNA 3D structure prediction. Retrospective evaluations on RNA-Puzzles and CASP15 natural RNA targets demonstrate RhoFold+'s superiority over existing methods, including human expert groups. Its efficacy and generalizability are further validated through cross-family and cross-type assessments, as well as time-censored benchmarks. Additionally, RhoFold+ predicts RNA secondary structures and inter-helical angles, providing empirically verifiable features that broaden its applicability to RNA structure and function studies.
Cite
@article{arxiv.2207.01586,
title = {Accurate RNA 3D structure prediction using a language model-based deep learning approach},
author = {Tao Shen and Zhihang Hu and Siqi Sun and Di Liu and Felix Wong and Jiuming Wang and Jiayang Chen and Yixuan Wang and Liang Hong and Jin Xiao and Liangzhen Zheng and Tejas Krishnamoorthi and Irwin King and Sheng Wang and Peng Yin and James J. Collins and Yu Li},
journal= {arXiv preprint arXiv:2207.01586},
year = {2025}
}
Comments
23 pages, 5 figures. A revised version is published in Nature Methods 21, 2287-2298 (2024). doi:10.1038/s41592-024-02487-0