Template-based RNA structure prediction advanced through a blind code competition

dc.contributor.authorLee, Youhan
dc.contributor.authorHe, Shujun
dc.contributor.authorOda, Toshiyuki
dc.contributor.authorRao, G. John
dc.contributor.authorKim, Yehyun
dc.contributor.authorKim, Raehyun
dc.contributor.authorKim, Hyunjin
dc.contributor.authorHeng, Cher Keng
dc.contributor.authorKowerko, Danny
dc.contributor.authorLi, Haowei
dc.contributor.authorNguyen, Hoa
dc.contributor.authorSampathkumar, Arunodhayan
dc.contributor.authorGomez, Raul Enrique
dc.contributor.authorChen, Meng
dc.contributor.authorYoshizawa, Atsushi
dc.contributor.authorKuraishi, Shun
dc.contributor.authorOgawa, Kenji
dc.contributor.authorZou, Shuxian
dc.contributor.authorPaullier, Alejo
dc.contributor.authorZhao, Bingkang
dc.contributor.authorChen, Huey-Long
dc.contributor.authorHsu, Tsu-An
dc.contributor.authorHirano, Tatsuya
dc.contributor.authorGezelle, Jeanine G.
dc.contributor.authorHaack, Daniel
dc.contributor.authorHong, Yibao
dc.contributor.authorJadhav, Shekhar
dc.contributor.authorKoirala, Deepak
dc.contributor.authorKretsch, Rachael C.
dc.contributor.authorLewicka, Anna
dc.contributor.authorLi, Shanshan
dc.contributor.authorMarcia, Marco
dc.contributor.authorPiccirilli, Joseph
dc.contributor.authorRudolfs, Boris
dc.contributor.authorSrivastava, Yoshita
dc.contributor.authorSteckelberg, Anna-Lena
dc.contributor.authorSu, Zhaoming
dc.contributor.authorToor, Navtej
dc.contributor.authorWang, Liu
dc.contributor.authorYang, Zi
dc.contributor.authorZhang, Kaiming
dc.contributor.authorZou, Jian
dc.contributor.authorBaker, David
dc.contributor.authorChen, Shi-Jie
dc.contributor.authorChiu, Wah
dc.contributor.authorDemkin, Maggie
dc.contributor.authorFavor, Andrew
dc.contributor.authorHummer, Alissa M.
dc.contributor.authorJoshi, Chaitanya K.
dc.contributor.authorKryshtafovych, Andriy
dc.contributor.authorKucukbenli, Emine
dc.contributor.authorMiao, Zhichao
dc.contributor.authorMoult, John
dc.contributor.authorMunley, Christian
dc.contributor.authorReade, Walter
dc.contributor.authorViel, Theo
dc.contributor.authorWesthof, Eric
dc.contributor.authorZhang, Sicheng
dc.contributor.authorDas, Rhiju
dc.date.accessioned2026-01-22T16:18:39Z
dc.date.issued2025-12-30
dc.description.abstractAutomatically predicting RNA 3D structure from sequence remains an unsolved challenge in biology and biotechnology. Here, we describe a Kaggle code competition engaging over 1700 teams and 43 previously unreleased structures to tackle this challenge. The top three submitted algorithms achieved scores within statistical error of the winners of the recent CASP16 competition. Unexpectedly, the top Kaggle strategy involved a pipeline for discovering 3D templates, without the use of deep learning. We integrated this template-modeling pipeline and other Kaggle strategies to develop a single model RNAPro that retrospectively outperformed individual Kaggle models on the same test set. These results suggest a growing importance of template-based modeling in RNA structure prediction.
dc.description.sponsorshipWe thank Elizabeth Park and Addison Howard (Kaggle) for administration of the Kaggle competition; Wei Huang (Case Western) for contributing CASP16 targets to seed the Public leaderboard; Stanford-SLAC Cryo-EM Center, U.C. Berkeley, ESRF CM01, and EMBL Heidelberg cryo-EM facilities for assistance and support in cryo-EM data collection; Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02- 06CH11357, for crystallography support; Hamish Blair, Ann Kladwang (Stanford), the NVIDIA DGX Cloud team and NAIRR Pilot (allocation NAIRR240281) for enabling release of RNet2 alpha during the competition; and the NHR high-performance computing facilities at TU Dresden (ZIH), available through the National High-Performance Computing Alliance (NHR; https://www.nhr-verein.de/unsere-partner) for computing support. We acknowledge funding from Howard Hughes Medical Institute (HHMI) (to R.D.), Stanford Medicine Endowed Faculty Scholar Award (to R.D.), Stanford School of Medicine Dean's Postdoctoral Fellowship (to A.M.H.), National Science Foundation (NSF CAREER award MCB2236996 to D.K.; GRFP DGE-2036197 to J.G.G.), A*STAR Singapore National Science Scholarship (to C.K.J.), Qualcomm Innovation Fellowship (to C.K.J.), Swedish National Research Council (VR, 2024-04107 to M.M.), HORIZON-MSCA-2023-DN-01 action (project: TargetRNA, n. 101168667 to M.M.), the Italian Association for Cancer Research ( IG 28746 to M.M.), Major Project of Guangzhou Laboratory (GZNL2024A01002, GZNL2023A01006, GZNL2025C01007, HWYQ23-003, YW-YFYJ0102 to Z.M.), the Natural Science Foundation of China (32270707 to Z.M., 32301044 and 32471301 to S.L., 32371345 to K.Z.), the Audacious Project at the Institute for Protein Design (to A.F. and D.B.), National Institutes of Health (R35GM150778 to A.-L.S.), and the National Key R&D Programs of China (2025YFE0200600, 2023YFF1204700, 2024YFF1206600 to Z.M. and 2022YFA1302700 to K.Z.). This article is subject to HHMI’s Open Access to Publications policy. HHMI lab heads have previously granted a nonexclusive CC BY 4.0 license to the public and a sublicensable license to HHMI in their research articles. Pursuant to those licenses, the author-accepted manuscript of this article can be made freely available under a CC BY 4.0 license immediately upon publication.
dc.description.urihttps://www.biorxiv.org/content/10.64898/2025.12.30.696949v1
dc.format.extent27 pages
dc.genrejournal articles
dc.genrepreprints
dc.identifierdoi:10.13016/m2tfgm-gxyx
dc.identifier.urihttps://doi.org/10.64898/2025.12.30.696949
dc.identifier.urihttp://hdl.handle.net/11603/41483
dc.language.isoen
dc.relation.isAvailableAtThe University of Maryland, Baltimore County (UMBC)
dc.relation.ispartofUMBC Staff Collection
dc.relation.ispartofUMBC Chemistry & Biochemistry Department
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleTemplate-based RNA structure prediction advanced through a blind code competition
dc.typeText
dcterms.creatorhttps://orcid.org/0000-0001-6424-3173

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