Fig. 1

In silico binding site similarity screen identifies tubulin-ER cross-reactivity. a The computational workflow of identifying and validating ligands binding to the taxane pocket of microtubules. Microenvironments of the taxane pocket were compared to a database of protein pocket microenvironments bound to small molecule ligands. The predicted candidate pockets with the optimal PocketFeature score (PFS < −3.5) were identified and ligands were tested using in vitro tubulin polymerization assay and in vivo cell-based assays. b Histogram indicating the distribution of PFS and the cumulative PFS of drug-binding pockets compared to the taxane site from the in silico pocket similarity screen. c Target enrichment analysis of the hits identified ER as the most frequent cognate receptor of ligands predicted to bind beta-tubulin