Children’s Nutrition Research Center Staff Publications

Language

English

Publication Date

7-1-2024

Journal

Nature Methods

DOI

10.1038/s41592-024-02321-7

PMID

38918604

PMCID

PMC11526832

PubMedCentral® Posted Date

1-1-2025

PubMedCentral® Full Text Version

Author MSS

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.

Keywords

Cryoelectron Microscopy, Ligands, Models, Molecular, SARS-CoV-2, COVID-19, Escherichia coli, beta-Galactosidase, Protein Conformation, Reproducibility of Results

Published Open-Access

yes

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