Accurate RNA 3D structure prediction using a language model-based deep learning approach

TL;DR

RhoFold+ is a novel deep learning approach utilizing a pre-trained RNA language model to accurately predict 3D structures of single-chain RNAs, addressing data scarcity and outperforming existing methods.

Contribution

The paper introduces RhoFold+, the first RNA 3D structure prediction method that integrates a large-scale RNA language model for improved accuracy and automation.

Findings

Outperforms existing RNA structure prediction methods on benchmarks.

Accurately predicts RNA secondary structures and inter-helical angles.

Demonstrates robustness across different RNA families and types.

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.