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Title: Evaluation of models determined by neutron diffraction and proposed improvements to their validation and deposition

Abstract

The Protein Data Bank (PDB) contains a growing number of models that have been determined using neutron diffraction or a hybrid method that combines X-ray and neutron diffraction. The advantage of neutron diffraction experiments is that the positions of all atoms can be determined, including H atoms, which are hardly detectable by X-ray diffraction. This allows the determination of protonation states and the assignment of H atoms to water molecules. Because neutrons are scattered differently by hydrogen and its isotope deuterium, neutron diffraction in combination with H/D exchange can provide information on accessibility, dynamics and chemical lability. In this study, the deposited data, models and model-to-data fit for all PDB entries that used neutron diffraction as the source of experimental data have been analysed. In many cases, the reported R work and R free values were not reproducible. In such cases, the model and data files were analysed to identify the reasons for this mismatch. The issues responsible for the discrepancies are summarized and explained. The analysis unveiled limitations to the annotation, deposition and validation of models and data, and a lack of community-wide accepted standards for the description of neutron models and data, as well as deficiencies in currentmore » model refinement tools. Most of the issues identified concern the handling of H atoms. Since the primary use of neutron macromolecular crystallography is to locate and directly visualize H atoms, it is important to address these issues, so that the deposited neutron models allow the retrieval of the maximum amount of information with the smallest effort of manual intervention. A path forward to improving the annotation, validation and deposition of neutron models and hybrid X-ray and neutron models is suggested.« less

Authors:
; ORCiD logo; ORCiD logo; ;
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
1461576
Alternate Identifier(s):
OSTI ID: 1477262
Grant/Contract Number:  
AC03-76SF00098; AC02-05CH11231
Resource Type:
Published Article
Journal Name:
Acta Crystallographica. Section D. Structural Biology
Additional Journal Information:
Journal Name: Acta Crystallographica. Section D. Structural Biology Journal Volume: 74 Journal Issue: 8; Journal ID: ISSN 2059-7983
Publisher:
International Union of Crystallography (IUCr)
Country of Publication:
United Kingdom
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; model validation; neutron crystallography; PDB data mining; H/D exchange; Phenix

Citation Formats

Liebschner, Dorothee, Afonine, Pavel V., Moriarty, Nigel W., Langan, Paul, and Adams, Paul D. Evaluation of models determined by neutron diffraction and proposed improvements to their validation and deposition. United Kingdom: N. p., 2018. Web. doi:10.1107/S2059798318004588.
Liebschner, Dorothee, Afonine, Pavel V., Moriarty, Nigel W., Langan, Paul, & Adams, Paul D. Evaluation of models determined by neutron diffraction and proposed improvements to their validation and deposition. United Kingdom. https://doi.org/10.1107/S2059798318004588
Liebschner, Dorothee, Afonine, Pavel V., Moriarty, Nigel W., Langan, Paul, and Adams, Paul D. Tue . "Evaluation of models determined by neutron diffraction and proposed improvements to their validation and deposition". United Kingdom. https://doi.org/10.1107/S2059798318004588.
@article{osti_1461576,
title = {Evaluation of models determined by neutron diffraction and proposed improvements to their validation and deposition},
author = {Liebschner, Dorothee and Afonine, Pavel V. and Moriarty, Nigel W. and Langan, Paul and Adams, Paul D.},
abstractNote = {The Protein Data Bank (PDB) contains a growing number of models that have been determined using neutron diffraction or a hybrid method that combines X-ray and neutron diffraction. The advantage of neutron diffraction experiments is that the positions of all atoms can be determined, including H atoms, which are hardly detectable by X-ray diffraction. This allows the determination of protonation states and the assignment of H atoms to water molecules. Because neutrons are scattered differently by hydrogen and its isotope deuterium, neutron diffraction in combination with H/D exchange can provide information on accessibility, dynamics and chemical lability. In this study, the deposited data, models and model-to-data fit for all PDB entries that used neutron diffraction as the source of experimental data have been analysed. In many cases, the reported R work and R free values were not reproducible. In such cases, the model and data files were analysed to identify the reasons for this mismatch. The issues responsible for the discrepancies are summarized and explained. The analysis unveiled limitations to the annotation, deposition and validation of models and data, and a lack of community-wide accepted standards for the description of neutron models and data, as well as deficiencies in current model refinement tools. Most of the issues identified concern the handling of H atoms. Since the primary use of neutron macromolecular crystallography is to locate and directly visualize H atoms, it is important to address these issues, so that the deposited neutron models allow the retrieval of the maximum amount of information with the smallest effort of manual intervention. A path forward to improving the annotation, validation and deposition of neutron models and hybrid X-ray and neutron models is suggested.},
doi = {10.1107/S2059798318004588},
journal = {Acta Crystallographica. Section D. Structural Biology},
number = 8,
volume = 74,
place = {United Kingdom},
year = {2018},
month = {7}
}

Journal Article:
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https://doi.org/10.1107/S2059798318004588

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