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Quantitative Structural Interpretation of Protein Crosslinks.

Title: Quantitative Structural Interpretation of Protein Crosslinks.
Authors: Filella-Merce I; Structural Bioinformatics Unit, Department of Structural Biology and Chemistry, Institut Pasteur, CNRS UMR3528, C3BI, USR3756 Paris, France; Faculty of Health and Life Sciences, University Pompeu Fabra, Carrer del Doctor Aiguader 80, Barcelona 08003, Spain.; Bardiaux B; Structural Bioinformatics Unit, Department of Structural Biology and Chemistry, Institut Pasteur, CNRS UMR3528, C3BI, USR3756 Paris, France.; Nilges M; Structural Bioinformatics Unit, Department of Structural Biology and Chemistry, Institut Pasteur, CNRS UMR3528, C3BI, USR3756 Paris, France.; Bouvier G; Structural Bioinformatics Unit, Department of Structural Biology and Chemistry, Institut Pasteur, CNRS UMR3528, C3BI, USR3756 Paris, France. Electronic address: guillaume.bouvier@pasteur.fr.
Source: Structure (London, England : 1993) [Structure] 2020 Jan 07; Vol. 28 (1), pp. 75-82.e4. Date of Electronic Publication: 2019 Nov 18.
Publication Type: Journal Article; Research Support, Non-U.S. Gov't
Language: English
Journal Info: Publisher: Cell Press Country of Publication: United States NLM ID: 101087697 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-4186 (Electronic) Linking ISSN: 09692126 NLM ISO Abbreviation: Structure Subsets: MEDLINE
Imprint Name(s): Publication: 2000- : Cambridge, Mass. : Cell Press; Original Publication: London : Current Biology, c1993-
MeSH Terms: Cross-Linking Reagents/*chemistry ; Proteins/*chemistry; Markov Chains ; Mass Spectrometry ; Models, Molecular ; Protein Conformation
Abstract: Chemical crosslinking, combined with mass spectrometry analysis, is a key source of information for characterizing the structure of large protein assemblies, in the context of molecular modeling. In most approaches, the interpretation is limited to simple spatial restraints, neglecting physico-chemical interactions between the crosslinker and the protein and their flexibility. Here we present a method, named NRGXL (new realistic grid for crosslinks), which models the flexibility of the crosslinker and the linked side-chains, by explicitly sampling many conformations. Also, the method can efficiently deal with overall protein dynamics. This method creates a physical model of the crosslinker and associated energy. A classifier based on it outperforms others, based on Euclidean distance or solvent-accessible distance and its efficiency makes it usable for validating 3D models from crosslinking data. NRGXL is freely available as a web server at: https://nrgxl.pasteur.fr.; (Copyright © 2019 Elsevier Ltd. All rights reserved.)
Contributed Indexing: Keywords: NRGXL; binary classification study; crosslinks; modeling; protein complexes; restraints; sampling
Substance Nomenclature: 0 (Cross-Linking Reagents); 0 (Proteins)
Entry Date(s): Date Created: 20191123 Date Completed: 20200930 Latest Revision: 20200930
Update Code: 20260130
DOI: 10.1016/j.str.2019.10.018
PMID: 31753619
Database: MEDLINE

Journal Article; Research Support, Non-U.S. Gov't