Abstract
Accurate quality assessment is critical for computational prediction and design of RNA three-dimensional (3D) structures, yet it remains a significant challenge. In this work, we introduce RNArank, a deep learning-based approach to both local and global quality assessment of predicted RNA 3D structure models. For a given structure model, RNArank extracts a comprehensive set of multi-modal features and processes them with a Y-shaped residual neural network. This network is trained to predict two intermediate 2D maps, including the inter-nucleotide contact map and the distance deviation map. These maps are then used to estimate the local and global accuracy. Extensive benchmark tests indicate that RNArank consistently outperforms traditional methods and other deep learning-based methods. Moreover, RNArank demonstrates promising performance in identifying high-quality structure models for targets from the recent CASP15 and CASP16 experiments. We anticipate that RNArank will serve as a valuable tool for the RNA biology community, improving the reliability of RNA structure modeling and thereby contributing to a deeper understanding of RNA function.
Similar content being viewed by others
Data availability
The authors declare that the data supporting the results and conclusions of this study are available within the paper and its Supplementary Information. The source data underlying Figs. 2–4 are provided in the Supplementary Data file. The test source data used in this study is available at Zenodo48 and our website (https://yanglab.qd.sdu.edu.cn/RNArank/benchmark/).
Code availability
The RNArank web server is available at: https://yanglab.qd.sdu.edu.cn/RNArank/. The source codes are available at Zenodo48 and GitHub (https://github.com/YangLab-SDU/RNArank/).
References
Kwon, D. RNA function follows form - why is it so hard to predict?. Nature 639, 1106–1108 (2025).
Madison, J. T., Everett, G. A. & Kung, H. Nucleotide sequence of a yeast tyrosine transfer RNA. Science 153, 531–534 (1966).
Levitt, M. Detailed molecular model for transfer ribonucleic acid. Nature 224, 759–763 (1969).
Sharma, S., Ding, F. & Dokholyan, N. V. iFoldRNA: three-dimensional RNA structure prediction and folding. Bioinformatics 24, 1951–1952 (2008).
Parisien, M. & Major, F. The MC-Fold and MC-Sym pipeline infers RNA structure from sequence data. Nature 452, 51–55 (2008).
Rother, M., Rother, K., Puton, T. & Bujnicki, J. M. ModeRNA: a tool for comparative modeling of RNA 3D structure. Nucleic Acids Res. 39, 4007–4022 (2011).
Zhao, Y. et al. Automated and fast building of three-dimensional RNA structures. Sci. Rep. 2, 734 (2012).
Popenda, M. et al. Automated 3D structure composition for large RNAs. Nucleic Acids Res. 40, e112 (2012).
Boniecki, M. J. et al. SimRNA: a coarse-grained method for RNA folding simulations and 3D structure prediction. Nucleic Acids Res. 44, e63 (2016).
Watkins, A. M., Rangan, R. & Das, R. FARFAR2: improved De Novo Rosetta prediction of complex global RNA folds. Structure 28, 963–976.e966 (2020).
Li, J., Zhang, S., Zhang, D. & Chen, S.-J. Vfold-Pipeline: a web server for RNA 3D structure prediction from sequences. Bioinformatics 38, 4042–4043 (2022).
Pearce, R., Omenn, G. S. & Zhang, Y. De Novo RNA tertiary structure prediction at atomic resolution using geometric potentials from deep learning. Preprint at bioRxiv https://www.biorxiv.org/content/10.1101/2022.05.15.491755v1 (2022).
Li, Y. et al. Integrating end-to-end learning with deep geometrical potentials for ab initio RNA structure prediction. Nat. Commun. 14, 5745 (2023).
Wang, W. et al. trRosettaRNA: automated prediction of RNA 3D structure with transformer network. Nat. Commun. 14, 7266 (2023).
Baek, M. et al. Accurate prediction of protein-nucleic acid complexes using RoseTTAFoldNA. Nat. Methods 21, 117–121 (2024).
Abramson, J. et al. Accurate structure prediction of biomolecular interactions with AlphaFold 3. Nature 630, 493–500 (2024).
Shen, T. et al. Accurate RNA 3D structure prediction using a language model-based deep learning approach. Nat. Methods 21, 2287–2298 (2024).
Wang, W., Peng, Z. & Yang, J. Predicting RNA 3D structure and conformers using a pre-trained secondary structure model and structure-aware attention. Preprint at bioRxiv https://www.biorxiv.org/content/10.1101/2025.04.09.647915v1 (2025).
Kagaya, Y. et al. NuFold: end-to-end approach for RNA tertiary structure prediction with flexible nucleobase center representation. Nat. Commun. 16, 881 (2025).
Li, Y., Feng, C., Zhang, X. & Zhang, Y. Ab initio RNA structure prediction with composite language model and denoised end-to-end learning. Preprint at bioRxiv https://www.biorxiv.org/content/10.1101/2025.03.05.641632v1 (2025).
Jumper, J. et al. Highly accurate protein structure prediction with AlphaFold. Nature 596, 583–589 (2021).
Schneider, B. et al. When will RNA get its AlphaFold moment?. Nucleic Acids Res. 51, 9522–9532 (2023).
Das, R. et al. Assessment of three-dimensional RNA structure prediction in CASP15. Proteins 91, 1747–1770 (2023).
Bu, F. et al. RNA-puzzles round V: blind predictions of 23 RNA structures. Nat. Methods 22, 399–411 (2025).
Kretsch, R. C. et al. Assessment of nucleic acid structure prediction in CASP16. Proteins https://doi.org/10.1002/prot.70072 (2025).
Tan, Y. L., Wang, X., Yu, S., Zhang, B. & Tan, Z. J. cgRNASP: coarse-grained statistical potentials with residue separation for RNA structure evaluation. NAR Genom. Bioinf. 5, lqad016 (2023).
Tan, Y. L., Wang, X., Shi, Y. Z., Zhang, W. & Tan, Z. J. rsRNASP: a residue-separation-based statistical potential for RNA 3D structure evaluation. Biophys. J. 121, 142–156 (2022).
Zhang, T., Hu, G., Yang, Y., Wang, J. & Zhou, Y. All-atom knowledge-based potential for RNA structure discrimination based on the distance-scaled finite ideal-gas reference state. J. Comput. Biol. 27, 856–867 (2020).
Townshend, R. J. L. et al. Geometric deep learning of RNA structure. Science 373, 1047–1051 (2021).
Li, J. et al. RNA3DCNN: local and global quality assessments of RNA 3D structures using 3D deep convolutional neural networks. PLoS Comput. Biol. 14, e1006514 (2018).
Tarafder, S. & Bhattacharya, D. lociPARSE: a locality-aware invariant point attention model for scoring RNA 3D structures. J. Chem. Inf. Model. 64, 8655–8664 (2024).
Mariani, V., Biasini, M., Barbato, A. & Schwede, T. lDDT: a local superposition-free score for comparing protein structures and models using distance difference tests. Bioinformatics 29, 2722–2728 (2013).
He, K., Zhang, X., Ren, S. & Sun, J. Deep residual learning for image recognition. In Proc. 2016 IEEE Conference on Computer Vision and Pattern Recognition (CVPR). 770–778 (IEEE, 2016).
Ballester, P. J., Finn, P. W. & Richards, W. G. Ultrafast shape recognition: evaluating a new ligand-based virtual screening technology. J. Mol. Graph. Model. 27, 836–845 (2009).
Hiranuma, N. et al. Improved protein structure refinement guided by deep learning based accuracy estimation. Nat. Commun. 12, 1340 (2021).
Guo, S. S., Liu, J., Zhou, X. G. & Zhang, G. J. DeepUMQA: ultrafast shape recognition-based protein model quality assessment using deep learning. Bioinformatics 38, 1895–1903 (2022).
Gong, S., Zhang, C. & Zhang, Y. RNA-align: quick and accurate alignment of RNA 3D structures based on size-independent TM-scoreRNA. Bioinformatics 35, 4459–4461 (2019).
Antczak, M. et al. New functionality of RNAComposer: an application to shape the axis of miR160 precursor structure. Acta Biochim. Polonica 63, 737–744 (2016).
Xiong, P., Wu, R., Zhan, J. & Zhou, Y. Pairing a high-resolution statistical potential with a nucleobase-centric sampling algorithm for improving RNA model refinement. Nat. Commun. 12, 2777 (2021).
Wang, W., Luo, Y., Peng, Z. & Yang, J. Accurate biomolecular structure prediction in CASP16 with optimized inputs to state-of-the-art predictors. Proteins https://doi.org/10.1002/prot.70030 (2025).
Zeng, C., Jian, Y., Vosoughi, S., Zeng, C. & Zhao, Y. Evaluating native-like structures of RNA-protein complexes through the deep learning method. Nat. Commun. 14, 1060 (2023).
Zhao, K., Zhao, P., Wang, S., Xia, Y. & Zhang, G. FoldPAthreader: predicting protein folding pathway using a novel folding force field model derived from known protein universe. Genome Biol. 25, 152 (2024).
Sarzynska, J., Popenda, M., Antczak, M. & Szachniuk, M. RNA tertiary structure prediction using RNAComposer in CASP15. Proteins 91, 1790–1799 (2023).
Fu, L., Niu, B., Zhu, Z., Wu, S. & Li, W. CD-HIT: accelerated for clustering the next-generation sequencing data. Bioinformatics 28, 3150–3152 (2012).
Páll, S. et al. Heterogeneous parallelization and acceleration of molecular dynamics simulations in GROMACS. J. Chem. Phys. 153, 134110 (2020).
Hofacker, I. L. Vienna RNA secondary structure server. Nucleic Acids Res. 31, 3429–3431 (2003).
Lorenz, R. et al. ViennaRNA Package 2.0. Algor. Mol. Biol. 6, 26 (2011).
Liu, X. et al. Source code and data for “Quality assessment of RNA 3D structure models using deep learning and intermediate 2D maps”. Zenodo, https://doi.org/10.5281/zenodo.17889848 (2025).
He, K., Zhang, X., Ren, S. & Sun, J. Identity mappings in deep residual networks. ECCV 2016, 630–645 (Springer, 2016).
Acknowledgements
This work is supported by the following funding sources: National Natural Science Foundation of China (NSFC T2225007, T2222012, 32430063, 62402075, 62501364), Postdoctoral Fellowship Program and China Postdoctoral Science Foundation (BX20240212, 2025M783122), the Science and Technology Research Program of Chongqing Municipal Education Commission (KJQN202300639), and Fundamental Research Funds for the Central Universities.
Author information
Authors and Affiliations
Contributions
J.Y. conceptualized and administered the study. X.L. designed and implemented the network. X.L., W.W., and J.Y. conducted the formal analysis. X.L., W.W., Z.D., and Z.W. performed data curation and generated decoys. Z.P. and W.W. co-supervised the study. All authors wrote and revised the manuscript.
Corresponding authors
Ethics declarations
Competing interests
The authors declare no competing interests.
Peer review
Peer review information
Communications Biology thanks the anonymous reviewers for their contribution to the peer review of this work. Primary Handling Editors: Xiangtao Li and Laura Rodríguez Pérez.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
About this article
Cite this article
Liu, X., Wang, W., Du, Z. et al. Quality assessment of RNA 3D structure models using deep learning and intermediate 2D maps. Commun Biol (2026). https://doi.org/10.1038/s42003-026-09582-2
Received:
Accepted:
Published:
DOI: https://doi.org/10.1038/s42003-026-09582-2


