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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 Laboratory (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 = {Tue Jul 24 00:00:00 EDT 2018},
month = {Tue Jul 24 00:00:00 EDT 2018}
}

Journal Article:
Free Publicly Available Full Text
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https://doi.org/10.1107/S2059798318004588

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Works referenced in this record:

Protein crystallography with spallation neutrons: the user facility at Los Alamos Neutron Science Center
journal, January 2004

  • Langan, Paul; Greene, Gayle; Schoenborn, Benno P.
  • Journal of Applied Crystallography, Vol. 37, Issue 1
  • DOI: 10.1107/S0021889803022891

Perdeuteration: improved visualization of solvent structure in neutron macromolecular crystallography
journal, November 2014

  • Fisher, S. J.; Blakeley, M. P.; Howard, E. I.
  • Acta Crystallographica Section D Biological Crystallography, Vol. 70, Issue 12
  • DOI: 10.1107/S1399004714021610

The IMAGINE instrument: first neutron protein structure and new capabilities for neutron macromolecular crystallography
journal, September 2013

  • Meilleur, Flora; Munshi, Parthapratim; Robertson, Lee
  • Acta Crystallographica Section D Biological Crystallography, Vol. 69, Issue 10
  • DOI: 10.1107/S0907444913019604

Neutron Laue diffraction study of concanavalin A The proton of Asp28
journal, January 1997

  • Habash, Jarjis; Raftery, James; Weisgerber, Susanne
  • Journal of the Chemical Society, Faraday Transactions, Vol. 93, Issue 24
  • DOI: 10.1039/a704143h

Neutron Crystal Structure of RAS GTPase Puts in Question the Protonation State of the GTP γ-Phosphate
journal, October 2015

  • Knihtila, Ryan; Holzapfel, Genevieve; Weiss, Kevin
  • Journal of Biological Chemistry, Vol. 290, Issue 52
  • DOI: 10.1074/jbc.M115.679860

Unambiguous determination of H-atom positions: comparing results from neutron and high-resolution X-ray crystallography
journal, April 2010

  • Gardberg, Anna S.; Del Castillo, Alexis Rae; Weiss, Kevin L.
  • Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 5
  • DOI: 10.1107/S0907444910005494

A systematic pairwise comparison of geometric parameters obtained by X-ray and neutron diffraction
journal, October 1986


Joint X-ray/Neutron Crystallographic Study of HIV-1 Protease with Clinical Inhibitor Amprenavir: Insights for Drug Design
journal, June 2013

  • Weber, Irene T.; Waltman, Mary Jo; Mustyakimov, Marat
  • Journal of Medicinal Chemistry, Vol. 56, Issue 13
  • DOI: 10.1021/jm400684f

Crystallization and preliminary neutron analysis of the dissimilatory sulfite reductase D (DsrD) protein from the sulfate-reducing bacterium Desulfovibrio vulgaris
journal, November 2003

  • Chatake, Toshiyuki; Mizuno, Nobuhiro; Voordouw, Gerrit
  • Acta Crystallographica Section D Biological Crystallography, Vol. 59, Issue 12
  • DOI: 10.1107/S0907444903020596

Large-volume protein crystal growth for neutron macromolecular crystallography
journal, March 2015

  • Ng, Joseph D.; Baird, James K.; Coates, Leighton
  • Acta Crystallographica Section F Structural Biology Communications, Vol. 71, Issue 4
  • DOI: 10.1107/S2053230X15005348

Neutron diffraction studies towards deciphering the protonation state of catalytic residues in the bacterial KDN9P phosphatase
journal, August 2013

  • Bryan, Tyrel; González, Javier M.; Bacik, John P.
  • Acta Crystallographica Section F Structural Biology and Crystallization Communications, Vol. 69, Issue 9
  • DOI: 10.1107/S1744309113021386

Hydration in proteins observed by high-resolution neutron crystallography
journal, January 2003

  • Chatake, Toshiyuki; Ostermann, Andreas; Kurihara, Kazuo
  • Proteins: Structure, Function, and Bioinformatics, Vol. 50, Issue 3
  • DOI: 10.1002/prot.10303

Neutron scattering lengths and cross sections
journal, January 1992


Comparative X-Ray and Neutron Diffraction Study of Bonding Effects in s-Triazine
journal, December 1967


Hydrogen atoms in proteins: Positions and dynamics
journal, August 2003

  • Engler, N.; Ostermann, A.; Niimura, N.
  • Proceedings of the National Academy of Sciences, Vol. 100, Issue 18
  • DOI: 10.1073/pnas.1834279100

Neutron and X-ray crystallographic analysis of the human α-thrombin–bivalirudin complex at pD 5.0: Protonation states and hydration structure of the enzyme–product complex
journal, August 2013

  • Yamada, Taro; Kurihara, Kazuo; Ohnishi, Yuki
  • Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, Vol. 1834, Issue 8
  • DOI: 10.1016/j.bbapap.2013.05.014

A new neutron single-crystal diffractometer dedicated for biological macromolecules (BIX-4)
journal, November 2003

  • Kurihara, Kazuo; Tanaka, Ichiro; Refai Muslih, Muhammad
  • Journal of Synchrotron Radiation, Vol. 11, Issue 1
  • DOI: 10.1107/S090904950302346X

Refinement of macromolecular structures against neutron data with SHELXL2013
journal, December 2013

  • Gruene, Tim; Hahn, Hinrich W.; Luebben, Anna V.
  • Journal of Applied Crystallography, Vol. 47, Issue 1
  • DOI: 10.1107/S1600576713027659

Joint X-ray and neutron refinement with phenix.refine
journal, October 2010

  • Afonine, Pavel V.; Mustyakimov, Marat; Grosse-Kunstleve, Ralf W.
  • Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 11
  • DOI: 10.1107/S0907444910026582

Studies of ribonuclease-A by X-ray and neutron diffraction
journal, August 1980

  • Wlodawer, A.
  • Acta Crystallographica Section B Structural Crystallography and Crystal Chemistry, Vol. 36, Issue 8
  • DOI: 10.1107/S0567740880007315

Neutron crystallographic study on rubredoxin from Pyrococcus furiosus by BIX-3, a single-crystal diffractometer for biomacromolecules
journal, July 2004

  • Kurihara, K.; Tanaka, I.; Chatake, T.
  • Proceedings of the National Academy of Sciences, Vol. 101, Issue 31
  • DOI: 10.1073/pnas.0403807101

The protein data bank: A computer-based archival file for macromolecular structures
journal, May 1977

  • Bernstein, Frances C.; Koetzle, Thomas F.; Williams, Graheme J. B.
  • Journal of Molecular Biology, Vol. 112, Issue 3
  • DOI: 10.1016/S0022-2836(77)80200-3

Cryogenic neutron protein crystallography: routine methods and potential benefits
journal, June 2014

  • Coates, Leighton; Tomanicek, Stephen; Schrader, Tobias E.
  • Journal of Applied Crystallography, Vol. 47, Issue 4
  • DOI: 10.1107/S1600576714010772

Structure of bovine pancreatic trypsin inhibitor
journal, December 1984


New analytical scattering-factor functions for free atoms and ions
journal, May 1995

  • Waasmaier, D.; Kirfel, A.
  • Acta Crystallographica Section A Foundations of Crystallography, Vol. 51, Issue 3
  • DOI: 10.1107/S0108767394013292

Large area neutron and X-ray image-plate detectors for macromolecular biology
journal, June 1997

  • Cipriani, F.; Castagna, J. -C; Claustre, L.
  • Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, Vol. 392, Issue 1-3
  • DOI: 10.1016/S0168-9002(97)00272-6

Neutron structure of type-III antifreeze protein allows the reconstruction of AFP-ice interface
journal, April 2011

  • Howard, Eduardo I.; Blakeley, Matthew P.; Haertlein, Michael
  • Journal of Molecular Recognition, Vol. 24, Issue 4
  • DOI: 10.1002/jmr.1130

Neutron Diffraction Analysis of Myoglobin
journal, October 1969


Bond lengths in organic and metal-organic compounds revisited: X —H bond lengths from neutron diffraction data
journal, May 2010

  • Allen, Frank H.; Bruno, Ian J.
  • Acta Crystallographica Section B Structural Science, Vol. 66, Issue 3
  • DOI: 10.1107/S0108768110012048

Neutron cryo-crystallography captures the protonation state of ferryl heme in a peroxidase
journal, July 2014


The Macromolecular Neutron Diffractometer MaNDi at the Spallation Neutron Source
journal, July 2015

  • Coates, Leighton; Cuneo, Matthew J.; Frost, Matthew J.
  • Journal of Applied Crystallography, Vol. 48, Issue 4
  • DOI: 10.1107/S1600576715011243

X-ray and neutron protein crystallographic analysis of the trypsin–BPTI complex
journal, January 2011

  • Kawamura, Kenji; Yamada, Taro; Kurihara, Kazuo
  • Acta Crystallographica Section D Biological Crystallography, Vol. 67, Issue 2
  • DOI: 10.1107/S0907444910053382

Low-barrier hydrogen bond in photoactive yellow protein
journal, January 2009

  • Yamaguchi, S.; Kamikubo, H.; Kurihara, K.
  • Proceedings of the National Academy of Sciences, Vol. 106, Issue 2
  • DOI: 10.1073/pnas.0811882106

Hydrogen and deuterium in myoglobin as seen by a neutron structure determination at 1.5 Å resolution
journal, March 2002


Near-Atomic Resolution Neutron Crystallography on Perdeuterated Pyrococcus furiosus Rubredoxin: Implication of Hydronium Ions and Protonation State Equilibria in Redox Changes
journal, December 2012

  • Cuypers, M. G.; Mason, S. A.; Blakeley, M. P.
  • Angewandte Chemie International Edition, Vol. 52, Issue 3
  • DOI: 10.1002/anie.201207071

Fifteen years of the Protein Crystallography Station: the coming of age of macromolecular neutron crystallography
journal, January 2017


An imaging plate neutron detector
journal, October 1994

  • Niimura, Nobuo; Karasawa, Yuuko; Tanaka, Inchiro
  • Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, Vol. 349, Issue 2-3
  • DOI: 10.1016/0168-9002(94)91220-3

Neutron crystallographic studies of T4 lysozyme at cryogenic temperature: Neutron Crystallographic Studies of T4 Lysozyme
journal, September 2017

  • Li, Le; Shukla, Shantanu; Meilleur, Flora
  • Protein Science, Vol. 26, Issue 10
  • DOI: 10.1002/pro.3231

Decacarbonyl-μ-hydrido-μ-vinyl- triangulo -triosmium: a combined X-ray and neutron diffraction study
journal, August 1978

  • Orpen, A. G.; Pippard, D.; Sheldrick, G. M.
  • Acta Crystallographica Section B Structural Crystallography and Crystal Chemistry, Vol. 34, Issue 8
  • DOI: 10.1107/S0567740878014697

Crystal structure refinement with SHELXL
journal, January 2015

  • Sheldrick, George M.
  • Acta Crystallographica Section C Structural Chemistry, Vol. 71, Issue 1, p. 3-8
  • DOI: 10.1107/S2053229614024218

Sub-atomic resolution X-ray crystallography and neutron crystallography: promise, challenges and potential
journal, June 2015


PHENIX: a comprehensive Python-based system for macromolecular structure solution
journal, January 2010

  • Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor
  • Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221
  • DOI: 10.1107/S0907444909052925

A procedure for joint refinement of macromolecular structures with X-ray and neutron diffraction data from single crystals
journal, March 1982


Automatic multiple-zone rigid-body refinement with a large convergence radius
journal, July 2009

  • Afonine, Pavel V.; Grosse-Kunstleve, Ralf W.; Urzhumtsev, Alexandre
  • Journal of Applied Crystallography, Vol. 42, Issue 4
  • DOI: 10.1107/S0021889809023528

Back-exchange of deuterium in neutron crystallography: characterization by IR spectroscopy
journal, March 2017

  • Yee, Ai Woon; Blakeley, Matthew P.; Moulin, Martine
  • Journal of Applied Crystallography, Vol. 50, Issue 2
  • DOI: 10.1107/S1600576717003624

Neutron crystallography: opportunities, challenges, and limitations
journal, October 2008

  • Blakeley, Matthew P.; Langan, Paul; Niimura, Nobuo
  • Current Opinion in Structural Biology, Vol. 18, Issue 5
  • DOI: 10.1016/j.sbi.2008.06.009

The Protein Data Bank
journal, January 2000


Macromolecular structure phasing by neutron anomalous diffraction
journal, August 2016

  • Cuypers, Maxime G.; Mason, Sax A.; Mossou, Estelle
  • Scientific Reports, Vol. 6, Issue 1
  • DOI: 10.1038/srep31487

The solvent component of macromolecular crystals
journal, April 2015

  • Weichenberger, Christian X.; Afonine, Pavel V.; Kantardjieff, Katherine
  • Acta Crystallographica Section D Biological Crystallography, Vol. 71, Issue 5
  • DOI: 10.1107/S1399004715006045

Generalized X-ray and neutron crystallographic analysis: more accurate and complete structures for biological macromolecules
journal, May 2009

  • Adams, Paul D.; Mustyakimov, Marat; Afonine, Pavel V.
  • Acta Crystallographica Section D Biological Crystallography, Vol. 65, Issue 6
  • DOI: 10.1107/S0907444909011548

BIODIFF: Diffractometer for large unit cells
journal, June 2015

  • Ostermann, Andresas; Schrader, Tobias
  • Journal of large-scale research facilities JLSRF, Vol. 1
  • DOI: 10.17815/jlsrf-1-19

Enhanced visibility of hydrogen atoms by neutron crystallography on fully deuterated myoglobin
journal, March 2000

  • Shu, F.; Ramakrishnan, V.; Schoenborn, B. P.
  • Proceedings of the National Academy of Sciences, Vol. 97, Issue 8
  • DOI: 10.1073/pnas.060024697