AlphaFold Protein Structure Database for Sequence-Independent Molecular Replacement
Abstract
Crystallographic phasing recovers the phase information that is lost during a diffraction experiment. Molecular replacement is a commonly used phasing method for crystal structures in the protein data bank. In one form it uses a protein sequence to search a structure database to find suitable templates for phasing. However, sequence information is not always available, such as when proteins are crystallized with unknown binding partner proteins or when the crystal is of a contaminant. The recent development of AlphaFold published the predicted protein structures for every protein from twenty distinct species. In this work, we tested whether AlphaFold-predicted E. coli protein structures were accurate enough to enable sequence-independent phasing of diffraction data from two crystallization contaminants of unknown sequence. Using each of more than 4000 predicted structures as a search model, robust molecular replacement solutions were obtained, which allowed the identification and structure determination of YncE and YadF. Our results demonstrate the general utility of the AlphaFold-predicted structure database with respect to sequence-independent crystallographic phasing.
- Publication Date:
- Research Org.:
- Brookhaven National Lab. (BNL), Upton, NY (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Biological and Environmental Research (BER); USDOE Office of Science (SC), Basic Energy Sciences (BES)
- OSTI Identifier:
- 1828309
- Report Number(s):
- BNL-222304-2021-JAAM
Journal ID: ISSN 2073-4352
- Grant/Contract Number:
- SC0012704
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Crystals
- Additional Journal Information:
- Journal Volume: 11; Journal Issue: 10; Journal ID: ISSN 2073-4352
- Publisher:
- MDPI
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; AlphaFold; molecular replacement; crystallization contaminants; structure determination
Citation Formats
Chai, Lawrence, Zhu, Ping, Chai, Jin, Pang, Changxu, Andi, Babak, McSweeney, Sean, Shanklin, John, and Liu, Qun. AlphaFold Protein Structure Database for Sequence-Independent Molecular Replacement. United States: N. p., 2021.
Web. doi:10.3390/cryst11101227.
Chai, Lawrence, Zhu, Ping, Chai, Jin, Pang, Changxu, Andi, Babak, McSweeney, Sean, Shanklin, John, & Liu, Qun. AlphaFold Protein Structure Database for Sequence-Independent Molecular Replacement. United States. https://doi.org/10.3390/cryst11101227
Chai, Lawrence, Zhu, Ping, Chai, Jin, Pang, Changxu, Andi, Babak, McSweeney, Sean, Shanklin, John, and Liu, Qun. Tue .
"AlphaFold Protein Structure Database for Sequence-Independent Molecular Replacement". United States. https://doi.org/10.3390/cryst11101227. https://www.osti.gov/servlets/purl/1828309.
@article{osti_1828309,
title = {AlphaFold Protein Structure Database for Sequence-Independent Molecular Replacement},
author = {Chai, Lawrence and Zhu, Ping and Chai, Jin and Pang, Changxu and Andi, Babak and McSweeney, Sean and Shanklin, John and Liu, Qun},
abstractNote = {Crystallographic phasing recovers the phase information that is lost during a diffraction experiment. Molecular replacement is a commonly used phasing method for crystal structures in the protein data bank. In one form it uses a protein sequence to search a structure database to find suitable templates for phasing. However, sequence information is not always available, such as when proteins are crystallized with unknown binding partner proteins or when the crystal is of a contaminant. The recent development of AlphaFold published the predicted protein structures for every protein from twenty distinct species. In this work, we tested whether AlphaFold-predicted E. coli protein structures were accurate enough to enable sequence-independent phasing of diffraction data from two crystallization contaminants of unknown sequence. Using each of more than 4000 predicted structures as a search model, robust molecular replacement solutions were obtained, which allowed the identification and structure determination of YncE and YadF. Our results demonstrate the general utility of the AlphaFold-predicted structure database with respect to sequence-independent crystallographic phasing.},
doi = {10.3390/cryst11101227},
journal = {Crystals},
number = 10,
volume = 11,
place = {United States},
year = {Tue Oct 12 00:00:00 EDT 2021},
month = {Tue Oct 12 00:00:00 EDT 2021}
}
Free Publicly Available Full Text
Publisher's Version of Record
Other availability
Search WorldCat to find libraries that may hold this journal
Save to My Library
You must Sign In or Create an Account in order to save documents to your library.
Works referenced in this record:
Crystallographic phasing from weak anomalous signals
journal, October 2015
- Liu, Qun; Hendrickson, Wayne A.
- Current Opinion in Structural Biology, Vol. 34
Anomalous diffraction in crystallographic phase evaluation
journal, February 2014
- Hendrickson, Wayne A.
- Quarterly Reviews of Biophysics, Vol. 47, Issue 1
An introduction to molecular replacement
journal, December 2007
- Evans, Philip; McCoy, Airlie
- Acta Crystallographica Section D Biological Crystallography, Vol. 64, Issue 1
The molecular replacement method
journal, February 1990
- Rossmann, M. G.
- Acta Crystallographica Section A Foundations of Crystallography, Vol. 46, Issue 2
MOLREP an Automated Program for Molecular Replacement
journal, December 1997
- Vagin, A.; Teplyakov, A.
- Journal of Applied Crystallography, Vol. 30, Issue 6, p. 1022-1025
Phaser crystallographic software
journal, July 2007
- McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Adams, Paul D.
- Journal of Applied Crystallography, Vol. 40, Issue 4
Implementation of molecular replacement in AMoRe
journal, September 2001
- Navaza, Jorge
- Acta Crystallographica Section D Biological Crystallography, Vol. 57, Issue 10
Recent developments in MrBUMP : better search-model preparation, graphical interaction with search models, and solution improvement and assessment
journal, March 2018
- Keegan, Ronan M.; McNicholas, Stuart J.; Thomas, Jens M. H.
- Acta Crystallographica Section D Structural Biology, Vol. 74, Issue 3
BALBES : a molecular-replacement pipeline
journal, December 2007
- Long, Fei; Vagin, Alexei A.; Young, Paul
- Acta Crystallographica Section D Biological Crystallography, Vol. 64, Issue 1
Phaser.MRage : automated molecular replacement
journal, October 2013
- Bunkóczi, Gábor; Echols, Nathaniel; McCoy, Airlie J.
- Acta Crystallographica Section D Biological Crystallography, Vol. 69, Issue 11
Macromolecular Modeling with Rosetta
journal, June 2008
- Das, Rhiju; Baker, David
- Annual Review of Biochemistry, Vol. 77, Issue 1
AMPLE : a cluster-and-truncate approach to solve the crystal structures of small proteins using rapidly computed ab initio models
journal, November 2012
- Bibby, Jaclyn; Keegan, Ronan M.; Mayans, Olga
- Acta Crystallographica Section D Biological Crystallography, Vol. 68, Issue 12
ContaMiner and ContaBase: a webserver and database for early identification of unwantedly crystallized protein contaminants
journal, November 2016
- Hungler, Arnaud; Momin, Afaque; Diederichs, Kay
- Journal of Applied Crystallography, Vol. 49, Issue 6
MoRDa , an automatic molecular replacement pipeline
journal, August 2015
- Vagin, Alexey; Lebedev, Andrey
- Acta Crystallographica Section A Foundations and Advances, Vol. 71, Issue a1
SIMBAD : a sequence-independent molecular-replacement pipeline
journal, June 2018
- Simpkin, Adam J.; Simkovic, Felix; Thomas, Jens M. H.
- Acta Crystallographica Section D Structural Biology, Vol. 74, Issue 7
Highly accurate protein structure prediction with AlphaFold
journal, July 2021
- Jumper, John; Evans, Richard; Pritzel, Alexander
- Nature
Protein structure prediction by AlphaFold 2: are attention and symmetries all you need?
journal, July 2021
- Bouatta, Nazim; Sorger, Peter; AlQuraishi, Mohammed
- Acta Crystallographica Section D Structural Biology, Vol. 77, Issue 8
Accurate prediction of protein structures and interactions using a three-track neural network
journal, July 2021
- Baek, Minkyung; DiMaio, Frank; Anishchenko, Ivan
- Science, Vol. 373, Issue 6557
Highly accurate protein structure prediction for the human proteome
journal, July 2021
- Tunyasuvunakool, Kathryn; Adler, Jonas; Wu, Zachary
- Nature, Vol. 596, Issue 7873
FMX – the Frontier Microfocusing Macromolecular Crystallography Beamline at the National Synchrotron Light Source II
journal, February 2021
- Schneider, Dieter K.; Shi, Wuxian; Andi, Babak
- Journal of Synchrotron Radiation, Vol. 28, Issue 2
Diffraction-geometry refinement in the DIALS framework
journal, March 2016
- Waterman, David G.; Winter, Graeme; Gildea, Richard J.
- Acta Crystallographica Section D Structural Biology, Vol. 72, Issue 4
How good are my data and what is the resolution?
journal, June 2013
- Evans, Philip R.; Murshudov, Garib N.
- Acta Crystallographica Section D Biological Crystallography, Vol. 69, Issue 7
Macromolecular microcrystallography
journal, April 2011
- Evans, Gwyndaf; Axford, Danny; Waterman, David
- Crystallography Reviews, Vol. 17, Issue 2
PyMDA : microcrystal data assembly using Python
journal, February 2020
- Takemaru, Lina; Guo, Gongrui; Zhu, Ping
- Journal of Applied Crystallography, Vol. 53, Issue 1
Sample manipulation and data assembly for robust microcrystal synchrotron crystallography
journal, April 2018
- Guo, Gongrui; Fuchs, Martin R.; Shi, Wuxian
- IUCrJ, Vol. 5, Issue 3
An approach to multi-copy search in molecular replacement
journal, December 2000
- Vagin, Alexei; Teplyakov, Alexei
- Acta Crystallographica Section D Biological Crystallography, Vol. 56, Issue 12
Features and development of Coot
journal, March 2010
- Emsley, P.; Lohkamp, B.; Scott, W. G.
- Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4
Towards automated crystallographic structure refinement with phenix.refine
journal, March 2012
- Afonine, Pavel V.; Grosse-Kunstleve, Ralf W.; Echols, Nathaniel
- Acta Crystallographica Section D Biological Crystallography, Vol. 68, Issue 4
Automated identification of elemental ions in macromolecular crystal structures
journal, March 2014
- Echols, Nathaniel; Morshed, Nader; Afonine, Pavel V.
- Acta Crystallographica Section D Biological Crystallography, Vol. 70, Issue 4
Robust structural analysis of native biological macromolecules from multi-crystal anomalous diffraction data
journal, June 2013
- Liu, Qun; Liu, Qinglian; Hendrickson, Wayne A.
- Acta Crystallographica Section D Biological Crystallography, Vol. 69, Issue 7
PROCHECK: a program to check the stereochemical quality of protein structures
journal, April 1993
- Laskowski, R. A.; MacArthur, M. W.; Moss, D. S.
- Journal of Applied Crystallography, Vol. 26, Issue 2
MolProbity : all-atom structure validation for macromolecular crystallography
journal, December 2009
- Chen, Vincent B.; Arendall, W. Bryan; Headd, Jeffrey J.
- Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 1
Structural basis for the DNA-binding activity of the bacterial β-propeller protein YncE
journal, November 2011
- Kagawa, Wataru; Sagawa, Tomohiko; Niki, Hironori
- Acta Crystallographica Section D Biological Crystallography, Vol. 67, Issue 12
Structural basis for Ca2+-dependent activation of a plant metacaspase
journal, May 2020
- Zhu, Ping; Yu, Xiao-Hong; Wang, Cheng
- Nature Communications, Vol. 11, Issue 1
Automated macromolecular model building for X-ray crystallography using ARP/wARP version 7
journal, June 2008
- Langer, Gerrit; Cohen, Serge X.; Lamzin, Victor S.
- Nature Protocols, Vol. 3, Issue 7
Crystal structure of E. coli β-carbonic anhydrase, an enzyme with an unusual pH-dependent activity
journal, May 2001
- Cronk, Jeff D.; Endrizzi, James A.; Cronk, Michelle R.
- Protein Science, Vol. 10, Issue 5
Identification of a Novel Noncatalytic Bicarbonate Binding Site in Eubacterial β-Carbonic Anhydrase
journal, March 2006
- Cronk, Jeff D.; Rowlett, Roger S.; Zhang, Kam Y. J.
- Biochemistry, Vol. 45, Issue 14
Protein purification and crystallization artifacts: The tale usually not told: Protein Purification and Crystallization Artifacts
journal, January 2016
- Niedzialkowska, Ewa; Gasiorowska, Olga; Handing, Katarzyna B.
- Protein Science, Vol. 25, Issue 3
On the combination of molecular replacement and single-wavelength anomalous diffraction phasing for automated structure determination
journal, September 2009
- Panjikar, Santosh; Parthasarathy, Venkataraman; Lamzin, Victor S.
- Acta Crystallographica Section D Biological Crystallography, Vol. 65, Issue 10