Interpreting chemical crosslinks: Score-based approaches and deep neural networks

Chemical cross-linking coupled with mass spectrometry (XL-MS) has become a powerful tool for probing residue-level proximities within macromolecular assemblies. By providing sparse but informative distance restraints, XL-MS can be integrated with electron microscopy and domain-level high-resolution structures to model the architecture of protein complexes. Unlike X-ray crystallography, electron microscopy, or solid-state Nuclear Magnetic Resonance (NMR), XL-MS can be applied under near-physiolog