Table 1.

Studies and Modeling Resources for Crosslink-Driven Protein Tertiary Structure Modeling

Study	Crosslinking/mass spectrometry	Data analysis	Protein structure modeling
Young et al. (2000) [10]	BS3 crosslinker with MALDI-postsource decay mass spectrometry	Automated Spectrum Assignment Program (ASAP)	Scoring of threaded models with crosslink constraints
Kahraman et al. (2011) [46]	Simulated crosslinks	Simulated crosslinks	XWalk algorithm for computing sSASD for crosslinks. Can be used for validation and visualization
Kahraman et al. (2013) [35]	Crosslink data from the literature	Crosslink data from the literature	Comparative modeling and de novo protocols using Rosetta [68]; XWalk [46] for validation
Hofmann et al. (2015) [49]	Simulated crosslinks	Simulated crosslinks	De novo modeling with fast arc length scoring of crosslinks for solvent-accessible surface approximation
Matthew Allen Bullock et al. (2016) [47]	Crosslink data from the literature [35]	Crosslink data from the literature [35]	JWalk algorithm for crosslink modeling using sSASD. Development of scoring metric that accounts for nonaccessible residues
Belsom et al. (2016) [18]	Sulfosuccinimidyl 4,4′-azipentanoate (sulfo-SDA) crosslinker with liquid chromatography–MS	Xi [27] for database search and XiFDR [33] for false discovery rate estimation	Guided model-based search [50] integrated into the Rosetta package [68]
Degiacomi et al. (2017) [48]	Crosslink data from the literature [35] and simulated crosslinks	Crosslink data from the literature [35] and simulated crosslinks	Crosslink modeling using shortest solvent-accessible distance and explicit modeling of protein flexibility (DynamXL)
Brodie et al. (2017) [64]	Several zero-length and short-range crosslinkers. Liquid chromatography–MS	Isotopically Coded Cleavable Cross-Linking Analysis Software Suite and Kojak [69]	Replica exchange discrete molecular dynamics