Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Joseph, Agnel Praveen, Olek, Mateusz, Malhotra, Sony, Zhang, Peijun, Cowtan, Kevin, Burnley, Tom, Winn, Martyn D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International Union of Crystallography 2022
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
_version_ 1784643217919049728
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
work_keys_str_mv AT josephagnelpraveen atomicmodelvalidationusingtheccpemsoftwaresuite
AT olekmateusz atomicmodelvalidationusingtheccpemsoftwaresuite
AT malhotrasony atomicmodelvalidationusingtheccpemsoftwaresuite
AT zhangpeijun atomicmodelvalidationusingtheccpemsoftwaresuite
AT cowtankevin atomicmodelvalidationusingtheccpemsoftwaresuite
AT burnleytom atomicmodelvalidationusingtheccpemsoftwaresuite
AT winnmartynd atomicmodelvalidationusingtheccpemsoftwaresuite