Fig. 4: Structural analysis.

a Binding mode of 1 as observed in the co-crystal structure with VHL (PDB code: 8P0F). 1 is color-coded by atom type with yellow carbons. b Superposition of the co-crystal structures of 1 (PDB code: 8P0F) and the game starting point reference molecule 1 in complex with VHL (PDB code: 5NVX, protein atoms not shown). Small molecules are color-coded by atom type with yellow and green carbons, respectively. c Superposition of the co-crystal structure of 1 and the original player-designed compound with the VHL protein coordinates used in the game (derived from 5NVX). Small molecules are color-coded by atom type and shown with yellow and blue carbons, respectively. d Superposition of the co-crystal structures of reference molecule 1 in complex with VHL and the player-designed compound. Small molecules are color-coded by atom type with green and blue carbons, respectively, and protein atoms are omitted.