RCSB Protein Data Bank and Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, Piscataway, NJ, USA.
Genome Center, University of California, Davis, CA, USA.
Nat Methods. 2024 Jul;21(7):1340-1348. doi: 10.1038/s41592-024-02321-7. Epub 2024 Jun 25.
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.
EMDataResource 配体模型挑战赛旨在评估在接近原子（1.9-2.5Å）分辨率下测定的冷冻电子显微镜（cryo-EM）图谱中结合蛋白和蛋白-核酸复合物的配体模型的可靠性和可重现性。选择了三个已发表的图谱作为目标：与抑制剂结合的大肠杆菌β-半乳糖苷酶、与共价结合的核苷酸类似物结合的 SARS-CoV-2 病毒 RNA 依赖性 RNA 聚合酶以及与结合脂质结合的 SARS-CoV-2 病毒离子通道 ORF3a。来自 17 个独立研究小组提交了 61 个模型，每个模型都有支持工作流程的详细信息。通过视觉检查和局部图谱质量、模型与图谱拟合、几何形状、能量和接触分数的量化来分析提交的配体模型和周围原子的质量。需要综合而不是单个分数来评估大分子+配体模型的质量。这些观察结果使我们建议了评估接近原子分辨率报道的配体结合大分子的 cryo-EM 结构的最佳实践。
