Fig. 5: Models predicted by NeuralPlexer, Chai-1, Boltz-1, and AlphaFold3 for the dopamine D3 receptor-eticlopride and GPR139-JNJ complexes.
From: AI meets physics in computational structure-based drug discovery for GPCRs
a, c The best ‘correctness’ models of the D3-eticlopride (a) and GPR139-JNJ-63353054 (c) complexes predicted by NeuralPLexer38 deviate quite substantially from the experimental structures and also feature a large number of steric clashes both within the receptor and between the receptor and the ligand. Clashes are determined using the Schrödinger suite Maestro and shown as orange and red dotted lines. Images were created with Maestro (Schrödinger release 2024-4, Schrödinger, LLC). (b, d, e–h) The best ‘correctness’ models of the D3 receptor-eticlopride (b, e, f) and GPR139-JNJ-63353054 (d, g, h) complexes predicted by Chai-146 (b, d), Boltz-152 (e, g), and AlphaFold340 (f, h) are free of gross steric inaccuracies and reasonably close to the experimental answer for most D3 predictions (b, e, f) but only some GPR139 predictions (g). The predicted ligand poses are shown in yellow sticks, the predicted protein models are shown in orange (D3 receptor, a, b, e, f) or green (GPR139, c–d, g–h) ribbons, whereas the experimental structures are in gray sticks and ribbons. Images were created with Maestro (Schrödinger release 2024-4, Schrödinger, LLC, New York, NY). i, j The distribution of geometric accuracy for the full ensemble of NeuralPLexer (cyan, 16 models per complex), Chai-1 (blue, 10 models per complex), Boltz-1 (violet, 15 models per complex), and AlphaFold3 (pink, 15 models per complex) models of D3 receptor-eticlopride (i) and GPR139-JNJ-63353054 (j) complexes. Each point represents a model or an experimental structure. The grey and yellow points represent experimental structures or GPCR Dock models (same as Fig. 3d-e), the shaded background represents the distribution of the plot parameters observed across high-resolution X-ray structures in the PDB; solid black curves represent isolines of the model ‘correctness’, measured as percentile of the experimentally observed distribution. Plots were created with ICM 3.9-3b161, https://www.molsoft.com/icm_browser.html.
