Quantitative Structural Interpretation of Protein Crosslinks

Isaac Filella-Merce (1, 2) , Benjamin Bardiaux (1) , Michael Nilges (1) , Guillaume Bouvier (1)

1 Bioinformatique structurale - Structural Bioinformatics
2 UPF - Universitat Pompeu Fabra [Barcelona]

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.

Keywords: Binary Classification study; Cross-links; restraints; protein complexes; NRGXL; sampling; modeling

Domains: Computer Science [cs]; Bioinformatics [q-bio.QM]; Computer Science [cs]; Information Theory [cs.IT]; Life Sciences [q-bio]; Biochemistry, Molecular Biology; Biochemistry [q-bio.BM]

Isaac Filella-Merce, Benjamin Bardiaux, Michael Nilges, Guillaume Bouvier. Quantitative Structural Interpretation of Protein Crosslinks. Structure, 2020, 28 (1), pp.75-82. ⟨10.1016/j.str.2019.10.018⟩. ⟨pasteur-02369173⟩