Outcomes of the EMDataResource cryo-EM ligand modeling challenge

DOI: 10.1038/s41592-024-02321-7

Authors: Catherine L. Lawson (The State University of New Jersey) , Andriy Kryshtafovych (University of California, Davis) , Grigore D. Pintilie (Stanford University) , Stephen Burley (Rutgers, The State University of New Jersey; University of California San Diego) , Jiří Černý (Institute of Biotechnology, Czech Academy of Sciences) , Vincent B. Chen (Duke University) , Paul Emsley (MRC Laboratory of Molecular Biology) , Alberto Gobbi (Genentech Inc) , Andrzej Joachimiak (Argonne National Laboratory; University of Chicago) , Sigrid Noreng (Genentech Inc) , Michael G. Prisant (Duke University) , Randy J. Read (University of Cambridge) , Jane S. Richardson (Duke University) , Alexis L. Rohou (Genentech Inc) , Bohdan Schneider (Institute of Biotechnology, Czech Academy of Sciences) , Benjamin D. Sellers (Genentech Inc) , Chenghua Shao (Rutgers, The State University of New Jersey) , Elizabeth Sourial (Chemical Computing Group) , Chris I. Williams (Chemical Computing Group) , Christopher J. Williams (Duke University) , Ying Yang (Genentech Inc) , Venkat Abbaraju (Rutgers, The State University of New Jersey) , Pavel V. Afonine (Lawrence Berkeley National Laboratory) , Matthew L. Baker (The University of Texas Health Science Center at Houston) , Paul S. Bond (University of York) , Tom L. Blundell (University of Cambridge) , Tom Burnley (UKRI Science and Technology Facilities Council) , Arthur Campbell (Broad Institute of MIT and Harvard) , Renzhi Cao (Pacific Lutheran University) , Jianlin Cheng (University of Missouri) , Grzegorz Chojnowski (European Molecular Biology Laboratory) , Kevin D. Cowtan (University of York) , Frank Dimaio (University of Washington) , Reza Esmaeeli (University of Florida) , Nabin Giri (University of Missouri) , Helmut Grubmüller (Max Planck Institute for Multidisciplinary Sciences) , Soon Wen Hoh (University of York) , Jie Hou (Saint Louis University) , Corey F. Hryc (The University of Texas Health Science Center at Houston) , Carola Hunte (University of Freiburg) , Maxim Igaev (Max Planck Institute for Multidisciplinary Sciences) , Agnel P. Joseph (UKRI Science and Technology Facilities Council, Research Complex at Harwell) , Wei-Chun Kao (University of Freiburg) , Daisuke Kihara (Purdue University) , Dilip Kumar (Ashoka University; Baylor College of Medicine) , Lijun Lang (University of Florida) , Sean Lin (University of Washington) , Sai R. Maddhuri Venkata Subramaniya (Purdue University) , Sumit Mittal (Arizona State University; VIT Bhopal University) , Arup Mondal (University of Florida) , Nigel W. Moriarty (Lawrence Berkeley National Laboratory) , Andrew Muenks (University of Washington) , Garib N. Murshudov (MRC Laboratory of Molecular Biology) , Robert A. Nicholls (MRC Laboratory of Molecular Biology; UKRI Science and Technology Facilities Council, Research Complex at Harwell) , Mateusz Olek (University of York; Diamond Light Source) , Colin M. Palmer (UKRI Science and Technology Facilities Council, Research Complex at Harwell) , Alberto Perez (University of Florida) , Emmi Pohjolainen (Max Planck Institute for Multidisciplinary Sciences) , Karunakar R. Pothula (Institute of Biological Information Processing (IBI-7, Structural Biochemistry) and Jülich Centre for Structural Biology (JuStruct), Forschungszentrum Jülich) , Christopher N. Rowley (Carleton University) , Daipayan Sarkar (Purdue University; Arizona State University) , Luisa U. Schäfer (Institute of Biological Information Processing (IBI-7, Structural Biochemistry) and Jülich Centre for Structural Biology (JuStruct), Forschungszentrum Jülich) , Christopher J. Schlicksup (Lawrence Berkeley National Laboratory) , Gunnar F. Schröder (Institute of Biological Information Processing (IBI-7, Structural Biochemistry) and Jülich Centre for Structural Biology (JuStruct), Forschungszentrum Jülich; University Düsseldorf) , Mrinal Shekhar (Broad Institute of MIT and Harvard; Arizona State University) , Dong Si (University of Washington) , Abhishek Singharoy (Arizona State University) , Oleg V. Sobolev (Lawrence Berkeley National Laboratory) , Genki Terashi (Purdue University) , Andrea C. Vaiana (Max Planck Institute for Multidisciplinary Sciences; Nature’s Toolbox (NTx)) , Sundeep C. Vedithi (University of Cambridge) , Jacob Verburgt (Purdue University) , Xiao Wang (Purdue University) , Rangana Warshamanage (MRC Laboratory of Molecular Biology) , Martyn Winn (UKRI Science and Technology Facilities Council, Research Complex at Harwell) , Simone Weyand (University of Cambridge) , Keitaro Yamashita (MRC Laboratory of Molecular Biology) , Minglei Zhao (University of Chicago) , Michael F. Schmid (SSRL, SLAC National Accelerator Laboratory) , Helen M. Berman (Rutgers, The State University of New Jersey; University of Southern California) , Wah Chiu (Stanford University; SSRL, SLAC National Accelerator Laboratory)
Co-authored by industrial partner: Yes

Type: Journal Paper
Journal: Nature Methods , VOL 24

State: Published (Approved)
Published: June 2024

Abstract: The EMDataResource Ligand Model Challenge aimed to assess the reliability and reproducibility of modeling ligands bound to protein and protein–nucleic acid complexes in cryogenic electron microscopy (cryo-EM) maps determined at near-atomic (1.9–2.5 Å) resolution. Three published maps were selected as targets: Escherichia coli beta-galactosidase with inhibitor, SARS-CoV-2 virus RNA-dependent RNA polymerase with covalently bound nucleotide analog and SARS-CoV-2 virus ion channel ORF3a with bound lipid. Sixty-one models were submitted from 17 independent research groups, each with supporting workflow details. The quality of submitted ligand models and surrounding atoms were analyzed by visual inspection and quantification of local map quality, model-to-map fit, geometry, energetics and contact scores. A composite rather than a single score was needed to assess macromolecule+ligand model quality. These observations lead us to recommend best practices for assessing cryo-EM structures of liganded macromolecules reported at near-atomic resolution.

Subject Areas: Technique Development, Biology and Bio-materials


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Added On: 03/07/2024 14:06

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Technique Development - Life Sciences & Biotech Structural biology Life Sciences & Biotech

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