Cross-link guided molecular modeling with ROSETTA.

Chemical cross-links identified by mass spectrometry generate distance restraints that reveal low-resolution structural information on proteins and protein complexes. The technology to reliably generate such data has become mature and robust enough to shift the focus to the question of how these dis...

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Autores principales: Abdullah Kahraman, Franz Herzog, Alexander Leitner, George Rosenberger, Ruedi Aebersold, Lars Malmström
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Publicado: Public Library of Science (PLoS) 2013
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Acceso en línea:https://doaj.org/article/3d4e1533f747432d843a487f147ebd2e
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spelling oai:doaj.org-article:3d4e1533f747432d843a487f147ebd2e2021-11-18T08:54:58ZCross-link guided molecular modeling with ROSETTA.1932-620310.1371/journal.pone.0073411https://doaj.org/article/3d4e1533f747432d843a487f147ebd2e2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24069194/?tool=EBIhttps://doaj.org/toc/1932-6203Chemical cross-links identified by mass spectrometry generate distance restraints that reveal low-resolution structural information on proteins and protein complexes. The technology to reliably generate such data has become mature and robust enough to shift the focus to the question of how these distance restraints can be best integrated into molecular modeling calculations. Here, we introduce three workflows for incorporating distance restraints generated by chemical cross-linking and mass spectrometry into ROSETTA protocols for comparative and de novo modeling and protein-protein docking. We demonstrate that the cross-link validation and visualization software Xwalk facilitates successful cross-link data integration. Besides the protocols we introduce XLdb, a database of chemical cross-links from 14 different publications with 506 intra-protein and 62 inter-protein cross-links, where each cross-link can be mapped on an experimental structure from the Protein Data Bank. Finally, we demonstrate on a protein-protein docking reference data set the impact of virtual cross-links on protein docking calculations and show that an inter-protein cross-link can reduce on average the RMSD of a docking prediction by 5.0 Å. The methods and results presented here provide guidelines for the effective integration of chemical cross-link data in molecular modeling calculations and should advance the structural analysis of particularly large and transient protein complexes via hybrid structural biology methods.Abdullah KahramanFranz HerzogAlexander LeitnerGeorge RosenbergerRuedi AebersoldLars MalmströmPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 9, p e73411 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Abdullah Kahraman
Franz Herzog
Alexander Leitner
George Rosenberger
Ruedi Aebersold
Lars Malmström
Cross-link guided molecular modeling with ROSETTA.
description Chemical cross-links identified by mass spectrometry generate distance restraints that reveal low-resolution structural information on proteins and protein complexes. The technology to reliably generate such data has become mature and robust enough to shift the focus to the question of how these distance restraints can be best integrated into molecular modeling calculations. Here, we introduce three workflows for incorporating distance restraints generated by chemical cross-linking and mass spectrometry into ROSETTA protocols for comparative and de novo modeling and protein-protein docking. We demonstrate that the cross-link validation and visualization software Xwalk facilitates successful cross-link data integration. Besides the protocols we introduce XLdb, a database of chemical cross-links from 14 different publications with 506 intra-protein and 62 inter-protein cross-links, where each cross-link can be mapped on an experimental structure from the Protein Data Bank. Finally, we demonstrate on a protein-protein docking reference data set the impact of virtual cross-links on protein docking calculations and show that an inter-protein cross-link can reduce on average the RMSD of a docking prediction by 5.0 Å. The methods and results presented here provide guidelines for the effective integration of chemical cross-link data in molecular modeling calculations and should advance the structural analysis of particularly large and transient protein complexes via hybrid structural biology methods.
format article
author Abdullah Kahraman
Franz Herzog
Alexander Leitner
George Rosenberger
Ruedi Aebersold
Lars Malmström
author_facet Abdullah Kahraman
Franz Herzog
Alexander Leitner
George Rosenberger
Ruedi Aebersold
Lars Malmström
author_sort Abdullah Kahraman
title Cross-link guided molecular modeling with ROSETTA.
title_short Cross-link guided molecular modeling with ROSETTA.
title_full Cross-link guided molecular modeling with ROSETTA.
title_fullStr Cross-link guided molecular modeling with ROSETTA.
title_full_unstemmed Cross-link guided molecular modeling with ROSETTA.
title_sort cross-link guided molecular modeling with rosetta.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/3d4e1533f747432d843a487f147ebd2e
work_keys_str_mv AT abdullahkahraman crosslinkguidedmolecularmodelingwithrosetta
AT franzherzog crosslinkguidedmolecularmodelingwithrosetta
AT alexanderleitner crosslinkguidedmolecularmodelingwithrosetta
AT georgerosenberger crosslinkguidedmolecularmodelingwithrosetta
AT ruediaebersold crosslinkguidedmolecularmodelingwithrosetta
AT larsmalmstrom crosslinkguidedmolecularmodelingwithrosetta
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