Fig. 3: Hsp90 as a practical example for fragment-based ligand generation.
From: Equivariant 3D-conditional diffusion model for molecular linker design
a, Experimentally identified fragments bound to separate subsites within the ATPase pocket of Hsp90 (PDB code 3HZ1). b, Starting fragments after removing methyl ester group. c, Crystal structure of the inhibitor reported in ref. 20 (PDB code 3HZ5). d, DiffLinker generated molecule that reproduces the reference inhibitor. e,f, Distributions of GNINA (e) and Vina (f) scores for unique samples generated by DiffLinker conditioned (green, n = 485) and unconditioned (blue, n = 166 for GNINA (e) and n = 66 for Vina (f) after removing outliers) on the target pocket. Red solid line depicts the score of the reference inhibitor reported in ref. 20. Magenta dashed lines represent scores for three DiffLinker samples that recover the reference inhibitor. For GNINA scores, higher values represent higher affinities.
