Figure reports the improvement in each 3D model's performance (R 2 ) compared to the corresponding 2D GNN when evaluated on the same test set. Figure compares the models when evaluated on the exact same test data for which conformers could be embedded. Due to the greater cost associated with training the 3D models, we focused on modeling only a subset of descriptors for which the 2D GNNs had relatively poor accuracy, especially properties exhibiting sensitivity to stereoelectronic or geometric effects. In general, we found that the 3D GNN-even when using MMFF94-level conformers-led to slight or substantial improvement in model accuracy for the majority of the modeled descriptors. The most significant improvements were observed for hydrogen atom NBO and NMR descriptors, Sterimol values, and amine pyramidalization. Only marginal improvement or diminished performance was observed for buried volumes, dipole moments, lone pair descriptors for the amines, and IR frequencies of the acids.