Structural prediction of protein models using distance restraints derived from cross-linking mass spectrometry data

This protocol describes a workflow for creating structural models of proteins or protein complexes using distance restraints derived from cross-linking mass spectrometry experiments. The distance restraints are used (i) to adjust preliminary models that are calculated on the basis of a homologous te...

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Published in:Nature protocols Vol. 13; no. 3; p. 478
Main Authors: Orbán-Németh, Zsuzsanna, Beveridge, Rebecca, Hollenstein, David M, Rampler, Evelyn, Stranzl, Thomas, Hudecz, Otto, Doblmann, Johannes, Schlögelhofer, Peter, Mechtler, Karl
Format: Journal Article
Language:English
Published: England Nature Publishing Group 01.03.2018
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ISSN:1754-2189, 1750-2799, 1750-2799
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Abstract This protocol describes a workflow for creating structural models of proteins or protein complexes using distance restraints derived from cross-linking mass spectrometry experiments. The distance restraints are used (i) to adjust preliminary models that are calculated on the basis of a homologous template and primary sequence, and (ii) to select the model that is in best agreement with the experimental data. In the case of protein complexes, the cross-linking data are further used to dock the subunits to one another to generate models of the interacting proteins. Predicting models in such a manner has the potential to indicate multiple conformations and dynamic changes that occur in solution. This modeling protocol is compatible with many cross-linking workflows and uses open-source programs or programs that are free for academic users and do not require expertise in computational modeling. This protocol is an excellent additional application with which to use cross-linking results for building structural models of proteins. The established protocol is expected to take 6-12 d to complete, depending on the size of the proteins and the complexity of the cross-linking data.
AbstractList This protocol describes a workflow for creating structural models of proteins or protein complexes using distance restraints derived from cross-linking mass spectrometry experiments. The distance restraints are used (i) to adjust preliminary models that are calculated on the basis of a homologous template and primary sequence, and (ii) to select the model that is in best agreement with the experimental data. In the case of protein complexes, the cross-linking data are further used to dock the subunits to one another to generate models of the interacting proteins. Predicting models in such a manner has the potential to indicate multiple conformations and dynamic changes that occur in solution. This modeling protocol is compatible with many cross-linking workflows and uses open-source programs or programs that are free for academic users and do not require expertise in computational modeling. This protocol is an excellent additional application with which to use cross-linking results for building structural models of proteins. The established protocol is expected to take 6-12 d to complete, depending on the size of the proteins and the complexity of the cross-linking data.
This protocol describes a workflow for creating structural models of proteins or protein complexes using distance restraints derived from cross-linking mass spectrometry experiments. The distance restraints are used (i) to adjust preliminary models that are calculated on the basis of a homologous template and primary sequence, and (ii) to select the model that is in best agreement with the experimental data. In the case of protein complexes, the cross-linking data are further used to dock the subunits to one another to generate models of the interacting proteins. Predicting models in such a manner has the potential to indicate multiple conformations and dynamic changes that occur in solution. This modeling protocol is compatible with many cross-linking workflows and uses open-source programs or programs that are free for academic users and do not require expertise in computational modeling. This protocol is an excellent additional application with which to use cross-linking results for building structural models of proteins. The established protocol is expected to take 6-12 d to complete, depending on the size of the proteins and the complexity of the cross-linking data.This protocol describes a workflow for creating structural models of proteins or protein complexes using distance restraints derived from cross-linking mass spectrometry experiments. The distance restraints are used (i) to adjust preliminary models that are calculated on the basis of a homologous template and primary sequence, and (ii) to select the model that is in best agreement with the experimental data. In the case of protein complexes, the cross-linking data are further used to dock the subunits to one another to generate models of the interacting proteins. Predicting models in such a manner has the potential to indicate multiple conformations and dynamic changes that occur in solution. This modeling protocol is compatible with many cross-linking workflows and uses open-source programs or programs that are free for academic users and do not require expertise in computational modeling. This protocol is an excellent additional application with which to use cross-linking results for building structural models of proteins. The established protocol is expected to take 6-12 d to complete, depending on the size of the proteins and the complexity of the cross-linking data.
Author Rampler, Evelyn
Orbán-Németh, Zsuzsanna
Hollenstein, David M
Stranzl, Thomas
Mechtler, Karl
Beveridge, Rebecca
Schlögelhofer, Peter
Doblmann, Johannes
Hudecz, Otto
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  givenname: Zsuzsanna
  surname: Orbán-Németh
  fullname: Orbán-Németh, Zsuzsanna
  organization: Mass Spectrometry and Protein Chemistry, Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna Biocenter (VBC), Vienna, Austria
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  givenname: Rebecca
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  fullname: Beveridge, Rebecca
  organization: Mass Spectrometry and Protein Chemistry, Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna Biocenter (VBC), Vienna, Austria
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  orcidid: 0000-0002-1977-1556
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  organization: Department of Biochemistry and Cell Biology, Max F. Perutz Laboratories, University of Vienna, Vienna, Austria
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  fullname: Rampler, Evelyn
  organization: Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Vienna, Austria
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  surname: Hudecz
  fullname: Hudecz, Otto
  organization: Mass Spectrometry and Protein Chemistry, Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna Biocenter (VBC), Vienna, Austria
– sequence: 7
  givenname: Johannes
  surname: Doblmann
  fullname: Doblmann, Johannes
  organization: Mass Spectrometry and Protein Chemistry, Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna Biocenter (VBC), Vienna, Austria
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  fullname: Schlögelhofer, Peter
  organization: Department of Chromosome Biology, Max F. Perutz Laboratories, University of Vienna, Vienna, Austria
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  givenname: Karl
  surname: Mechtler
  fullname: Mechtler, Karl
  organization: Mass Spectrometry and Protein Chemistry, Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna Biocenter (VBC), Vienna, Austria
BackLink https://www.ncbi.nlm.nih.gov/pubmed/29419816$$D View this record in MEDLINE/PubMed
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References 29942005 - Nat Protoc. 2018 Jul;13(7):1503. doi: 10.1038/s41596-018-0017-6.
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Snippet This protocol describes a workflow for creating structural models of proteins or protein complexes using distance restraints derived from cross-linking mass...
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SubjectTerms Amino acid sequence
Computer applications
Computer Simulation
Constraints
Cross-Linking Reagents - chemistry
Crosslinking
Data processing
Forecasting - methods
Homology
Mass spectrometry
Mass Spectrometry - methods
Mass spectroscopy
Mathematical models
Models, Molecular
Predictions
Protein Structure, Tertiary - genetics
Protein Structure, Tertiary - physiology
Proteins
Proteins - genetics
Proteins - physiology
Scientific imaging
Source programs
Spectroscopy
Structural models
Workflow
Title Structural prediction of protein models using distance restraints derived from cross-linking mass spectrometry data
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