10.1002/(ISSN)1097-0134 PROT Proteins: Structure, Function, and Bioinformatics Proteins 0887-3585 1097-0134 John Wiley & Sons, Inc. Hoboken, USA 10.1002/prot.70035 PROT70035 Prot-00195-2025.R1 RESEARCH ARTICLE RESEARCH ARTICLE Highlights of Model Quality Assessment in CASP16 Fadini Alisia https://orcid.org/0000-0001-5246-9124 1 Adiyaman Recep https://orcid.org/0000-0001-8124-5381 2 Alhaddad Shaima N. https://orcid.org/0009-0001-1937-0373 2 Behzadi Behnosh https://orcid.org/0009-0008-8980-0894 2 Cheng Jianlin https://orcid.org/0000-0003-0305-2853 3 Cui Xinyue https://orcid.org/0009-0005-6015-2449 4 Edmunds Nicholas S. https://orcid.org/0000-0002-7238-6008 2 Freddolino Lydia https://orcid.org/0000-0002-5821-4226 5 6 Genc Ahmet G. https://orcid.org/0009-0001-7195-9353 2 Liang Fang https://orcid.org/0009-0006-4834-5755 4 Liu Dong https://orcid.org/0009-0003-8512-9005 4 Liu Jian https://orcid.org/0000-0002-7570-8690 3 Liu Quancheng https://orcid.org/0009-0004-8207-2629 6 McGuffin Liam J. https://orcid.org/0000-0003-4501-4767 2 Neupane Pawan https://orcid.org/0009-0008-5283-4951 3 Peng Chunxiang https://orcid.org/0009-0006-9735-0278 5 Shortle David R. https://orcid.org/0009-0009-4903-5865 7 Sun Meng https://orcid.org/0009-0002-7123-7788 4 Wang Haodong https://orcid.org/0009-0000-1896-9408 4 Wuyun Qiqige https://orcid.org/0000-0002-7228-903X 8 Zhang Guijun https://orcid.org/0000-0002-7815-5884 4 Zhao Xuanfeng https://orcid.org/0009-0005-0455-9500 4 Zheng Wei https://orcid.org/0000-0002-2984-9003 6 9 Read Randy J. https://orcid.org/0000-0001-8273-0047 rjr27@cam.ac.uk * 1 Cambridge Institute for Medical Research, University of Cambridge Cambridge UK School of Biological Sciences University of Reading Reading UK Department of Electrical Engineering and Computer Science University of Missouri Columbia Missouri USA College of Information Engineering, Zhejiang University of Technology Hangzhou China Department of Biological Chemistry University of Michigan Ann Arbor Michigan USA Department of Computational Medicine and Bioinformatics University of Michigan Ann Arbor Michigan USA Department of Biological Chemistry Johns Hopkins University School of Medicine Baltimore Maryland USA Department of Computer Science and Engineering Michigan State University East Lansing Michigan USA NITFID, School of Statistics and Data Science, AAIS, LPMC and KLMDASR Nankai University Tianjin China Correspondence: Randy J. Read (rjr27@cam.ac.uk) 14 08 2025 28 07 2025 15 04 2025 30 07 2025 © 2025 Wiley Periodicals LLC. © 2025 The Author(s). PROTEINS: Structure, Function, and Bioinformatics published by Wiley Periodicals LLC. 2025 © 2025 The Author(s). PROTEINS: Structure, Function, and Bioinformatics published by Wiley Periodicals LLC. http://creativecommons.org/licenses/by/4.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. ABSTRACT

Model quality assessment (MQA) remains a critical component of structural bioinformatics for both structure predictors and experimentalists seeking to use predictions for downstream applications. In CASP16, the Evaluation of Model Accuracy (EMA) category featured both global and local quality estimation for multimeric assemblies (QMODE1 and QMODE2), as well as a novel QMODE3 challenge—requiring predictors to identify the best five models from thousands generated by MassiveFold. This paper presents detailed results from several leading CASP16 EMA methods, highlighting the strengths and limitations of the approaches.

 computational molecular biology molecular models protein conformation protein domains National Natural Science Foundation of China 10.13039/501100001809 12426303 62173304 Tianjin Science and Technology Program 10.13039/501100019065 24ZXZSSS00320 National Institute of Allergy and Infectious Diseases 10.13039/100000060 AI134678 National Science Foundation 10.13039/100000001 MTM2025426 DBI2308699 Pioneer and Leading Goose R&D Program of Zhejiang Zhejiang Province High‐level Talent Special Support Program 2023R5248 Fundamental Research Funds for the Central Universities 10.13039/501100012226 054‐63253109 National Key Research and Development Program of China 10.13039/501100012166 2022ZD0115103 Biotechnology and Biological Sciences Research Council 10.13039/501100000268 BB/Y009398/1 BB/T018496/1 Wellcome Trust 10.13039/100010269 209407/Z/17/Z Republic of Turkey Ministry of National Education U.S. National Science Foundation 10.13039/100000001 2138259 2138286 2138307 2137603 2138296 National Institutes of Health (USA) 10.13039/100000002 Kuwaiti Government “Pioneer” and “Leading Goose” R&D Program of Zhejiang 2025C01190 US National Institute of General Medical Sciences (NIGMS/NIH) R01GM100482 David R Shortle Protein Research Fund US National Institute of Health R01GM093123