Incorrect Aromaticity and Planarity Interpretation for Bicyclic Molecule

[Jnelen]

I have encountered a problem with the way the software interprets the structure of a bicyclic molecule, leading to incorrect results in the output. Specifically, the molecule in question consists of a bicyclic structure where only one of the rings is aromatic. However, during processing, both rings are incorrectly interpreted as aromatic. Additionally, the non-aromatic ring is also treated as planar, which is not chemically accurate and affects downstream results when working with this ligand in complex with a protein.

For example, consider the structure of the input molecule shown below:

When this ligand is processed with the protein, the output structure incorrectly identifies both rings as aromatic and planar. You can see my result here:

To reproduce the issue, you can use the attached Fasta file along with the ligand structure provided in either the regular aromatic SMILES format or the kekule format (explicit double bonds). I have tried both, but the results remain the same in both cases. The input and output files are included in the attached zip file for your convenience: boltz_aromaticity.zip

[gcorso]

Thank you for sharing this finding @Jnelen!

Currently, the model (similarly to AlphaFold3) does not take as input information about whether the bonds are single/double/aromatic so changing the input is not indeed supposed to change the output.

We are experimenting with different ways of fine-tuning the model to solve some of these issues and will share improvements as soon as we find them!

[Jnelen]

Thank you for sharing this finding @Jnelen!

Currently, the model (similarly to AlphaFold3) does not take as input information about whether the bonds are single/double/aromatic so changing the input is not indeed supposed to change the output.

We are experimenting with different ways of fine-tuning the model to solve some of these issues and will share improvements as soon as we find them!

Thanks a lot for the clarification! Looking forward to seeing the future improvements and evolution of this exciting project!