Overview and applications of map and model validation tools in the CCP-EM software suite. (2nd August 2022)

• Record Type: Journal Article
• Authors: Joseph, Agnel Praveen; Malhotra, Sony; Burnley, Tom; Winn, Martyn D.
• Is Part Of: Faraday discussions. Volume 240(2022)
• Page Start: 196
• Page End: 209
• Publication Date: 2022-08-02
• Subjects: Chemistry -- Periodicals; Metallurgy -- Periodicals; Electrochemistry -- Periodicals; 540
• DOI: 10.1039/d2fd00103a
• Languages: English
• ISSNs: 1359-6640

Abstract

Abstract : Atomic models from cryo-EM show a preference for geometric quality with the expense of agreement with the map data. This study highlights the lack of validation standards and CCP-EM efforts and related developments in this context. Abstract : Cryogenic electron microscopy (cryo-EM) has recently been established as a powerful technique for solving macromolecular structures. Although the best resolutions achievable are improving, a significant majority of data are still resolved at resolutions worse than 3 Å, where it is non-trivial to build or fit atomic models. The map reconstructions and atomic models derived from the maps are also prone to errors accumulated through the different stages of data processing. Here, we highlight the need to evaluate both model geometry and fit to data at different resolutions. Assessment of cryo-EM structures from SARS-CoV-2 highlights a bias towards optimising the model geometry to agree with the most common conformations, compared to the agreement with data. We present the CoVal web service which provides multiple validation metrics to reflect the quality of atomic models derived from cryo-EM data of structures from SARS-CoV-2. We demonstrate that further refinement can lead to improvement of the agreement with data without the loss of geometric quality. We also discuss the recent CCP-EM developments aimed at addressing some of the current shortcomings.