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Atomic model validation using the CCP-EM software suite
Recently, there has been a dramatic improvement in the quality and quantity of data derived using cryogenic electron microscopy (cryo-EM). This is also associated with a large increase in the number of atomic models built. Although the best resolutions that are achievable are improving, often the lo...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
International Union of Crystallography
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8805302/ https://www.ncbi.nlm.nih.gov/pubmed/35102881 http://dx.doi.org/10.1107/S205979832101278X |
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author | Joseph, Agnel Praveen Olek, Mateusz Malhotra, Sony Zhang, Peijun Cowtan, Kevin Burnley, Tom Winn, Martyn D. |
author_facet | Joseph, Agnel Praveen Olek, Mateusz Malhotra, Sony Zhang, Peijun Cowtan, Kevin Burnley, Tom Winn, Martyn D. |
author_sort | Joseph, Agnel Praveen |
collection | PubMed |
description | Recently, there has been a dramatic improvement in the quality and quantity of data derived using cryogenic electron microscopy (cryo-EM). This is also associated with a large increase in the number of atomic models built. Although the best resolutions that are achievable are improving, often the local resolution is variable, and a significant majority of data are still resolved at resolutions worse than 3 Å. Model building and refinement is often challenging at these resolutions, and hence atomic model validation becomes even more crucial to identify less reliable regions of the model. Here, a graphical user interface for atomic model validation, implemented in the CCP-EM software suite, is presented. It is aimed to develop this into a platform where users can access multiple complementary validation metrics that work across a range of resolutions and obtain a summary of evaluations. Based on the validation estimates from atomic models associated with cryo-EM structures from SARS-CoV-2, it was observed that models typically favor adopting the most common conformations over fitting the observations when compared with the model agreement with data. At low resolutions, the stereochemical quality may be favored over data fit, but care should be taken to ensure that the model agrees with the data in terms of resolvable features. It is demonstrated that further re-refinement can lead to improvement of the agreement with data without the loss of geometric quality. This also highlights the need for improved resolution-dependent weight optimization in model refinement and an effective test for overfitting that would help to guide the refinement process. |
format | Online Article Text |
id | pubmed-8805302 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | International Union of Crystallography |
record_format | MEDLINE/PubMed |
spelling | pubmed-88053022022-02-09 Atomic model validation using the CCP-EM software suite Joseph, Agnel Praveen Olek, Mateusz Malhotra, Sony Zhang, Peijun Cowtan, Kevin Burnley, Tom Winn, Martyn D. Acta Crystallogr D Struct Biol Ccp4 Recently, there has been a dramatic improvement in the quality and quantity of data derived using cryogenic electron microscopy (cryo-EM). This is also associated with a large increase in the number of atomic models built. Although the best resolutions that are achievable are improving, often the local resolution is variable, and a significant majority of data are still resolved at resolutions worse than 3 Å. Model building and refinement is often challenging at these resolutions, and hence atomic model validation becomes even more crucial to identify less reliable regions of the model. Here, a graphical user interface for atomic model validation, implemented in the CCP-EM software suite, is presented. It is aimed to develop this into a platform where users can access multiple complementary validation metrics that work across a range of resolutions and obtain a summary of evaluations. Based on the validation estimates from atomic models associated with cryo-EM structures from SARS-CoV-2, it was observed that models typically favor adopting the most common conformations over fitting the observations when compared with the model agreement with data. At low resolutions, the stereochemical quality may be favored over data fit, but care should be taken to ensure that the model agrees with the data in terms of resolvable features. It is demonstrated that further re-refinement can lead to improvement of the agreement with data without the loss of geometric quality. This also highlights the need for improved resolution-dependent weight optimization in model refinement and an effective test for overfitting that would help to guide the refinement process. International Union of Crystallography 2022-01-24 /pmc/articles/PMC8805302/ /pubmed/35102881 http://dx.doi.org/10.1107/S205979832101278X Text en © Agnel Praveen Joseph et al. 2022 https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited. |
spellingShingle | Ccp4 Joseph, Agnel Praveen Olek, Mateusz Malhotra, Sony Zhang, Peijun Cowtan, Kevin Burnley, Tom Winn, Martyn D. Atomic model validation using the CCP-EM software suite |
title | Atomic model validation using the CCP-EM software suite |
title_full | Atomic model validation using the CCP-EM software suite |
title_fullStr | Atomic model validation using the CCP-EM software suite |
title_full_unstemmed | Atomic model validation using the CCP-EM software suite |
title_short | Atomic model validation using the CCP-EM software suite |
title_sort | atomic model validation using the ccp-em software suite |
topic | Ccp4 |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8805302/ https://www.ncbi.nlm.nih.gov/pubmed/35102881 http://dx.doi.org/10.1107/S205979832101278X |
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