When using the 3D Ligand Based Score in a generator, the generated molecules are optimized with respect to a crystallized reference molecule using two 3D scores: the 3D Shape Similarity and 3D Pharmacophore Similarity.
The model generates initial poses using our Flow Matching algorithm. These poses are then refined and optimized under shape, pharmacophore, and internal-energy constraints.
3D Shape Score
The 3D Shape Similarity corresponds to the Shape Tanimoto Distance, which is a ratio of volume overlap between the reference compound and the generated molecule. It is calculated as an "Intersection over Union":
where O represents the volume of a molecule, A and B are two different molecules, and AB is the overlap between both molecules.
References
For more information, please check the following NeurIPS paper:
Template-Guided 3D Molecular Pose Generation via Flow Matching and Differentiable Optimization
Also available as a preprint: https://arxiv.org/abs/2506.06305