Quantitative Structural Interpretation of Protein Crosslinks. 2020

Isaac Filella-Merce, and Benjamin Bardiaux, and Michael Nilges, and Guillaume Bouvier
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.

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.

UI MeSH Term Description Entries
D008390 Markov Chains A stochastic process such that the conditional probability distribution for a state at any future instant, given the present state, is unaffected by any additional knowledge of the past history of the system. Markov Process,Markov Chain,Chain, Markov,Chains, Markov,Markov Processes,Process, Markov,Processes, Markov
D008958 Models, Molecular Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures. Molecular Models,Model, Molecular,Molecular Model
D011487 Protein Conformation The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). Conformation, Protein,Conformations, Protein,Protein Conformations
D011506 Proteins Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein. Gene Products, Protein,Gene Proteins,Protein,Protein Gene Products,Proteins, Gene
D003432 Cross-Linking Reagents Reagents with two reactive groups, usually at opposite ends of the molecule, that are capable of reacting with and thereby forming bridges between side chains of amino acids in proteins; the locations of naturally reactive areas within proteins can thereby be identified; may also be used for other macromolecules, like glycoproteins, nucleic acids, or other. Bifunctional Reagent,Bifunctional Reagents,Cross Linking Reagent,Crosslinking Reagent,Cross Linking Reagents,Crosslinking Reagents,Linking Reagent, Cross,Linking Reagents, Cross,Reagent, Bifunctional,Reagent, Cross Linking,Reagent, Crosslinking,Reagents, Bifunctional,Reagents, Cross Linking,Reagents, Cross-Linking,Reagents, Crosslinking
D013058 Mass Spectrometry An analytical method used in determining the identity of a chemical based on its mass using mass analyzers/mass spectrometers. Mass Spectroscopy,Spectrometry, Mass,Spectroscopy, Mass,Spectrum Analysis, Mass,Analysis, Mass Spectrum,Mass Spectrum Analysis,Analyses, Mass Spectrum,Mass Spectrum Analyses,Spectrum Analyses, Mass

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