Fig. 4: Polypharmacology compounds targeting ten synthetic-lethal interactions.
From: De novo generation of multi-target compounds using deep generative chemistry
a Synthetic-lethal interactions reported previously in human cancer cells (see text). Color corresponds to protein class: histone binding proteins are shown in green, serine/threonine kinases are blue, tyrosine kinases are red, and DNA binding proteins are purple. b Molecular docking analysis of POLYGON-generated compounds against each of the ten protein pairs from (a). Plots for each protein pair are arranged in a (5 × 2) grid. Each plot shows the distribution of binding activation energies for the docking configurations of 100 polypharmacology compounds generated by POLYGON (red) versus 100 randomly selected ligands from BindingDB (gray). For each target pair, the ΔG activation energies of POLYGON-generated compounds against each target were significantly more favorable (negative) than for compounds randomly drawn from BindingDB (p < 1 × 10−5 by one-sided t test). Source data are provided as a Source Data file.
