Extended Data Fig. 7: Bioinformatic analysis of probed tryptophan sites and proteins.

a) Venn diagram of proteins identified by DADPS biotin or desthiobiotin probes, where a total of 591 proteins were targeted by Trp-CLiC. b) Comparison of targeted proteins with the phase-separated protein database list, revealing overlapped 51 targeted proteins were reported to be phase-separated. c) Comparison of targeted proteins with the membrane-less organelle protein list, where 65.5% of targeted proteins were located in diverse membrane-less organelles. d) Drug Bank analysis of the identified 591 proteins with hyperreactive tryptophan residues, showing that 64% of them are currently classified as non-druggable. e) Gene Ontology biological pathway enrichment analysis of these 591 proteins, showing that RNA metabolism and processes pathways were significantly enriched. f) Four interaction modes of targeted tryptophans analysed by AlphaFold structure screening. g) The Trp-CLiC method revealed hyperreactive tryptophan sites, with W6 on DDX19B, W422 on FXR1, W271 on CAPZA1, and W14 on ABCF1 as representative examples. Solvent accessibilities of tryptophan residues in these three target proteins were analysed by the Discovery Studio program, indicating that the most surface-exposed tryptophan sites were probed whereas other tryptophan residues were not labelled.