Measuring Chemical LLM robustness to molecular representations: a SMILES variation-based framework

Journal of Cheminformatics. 2025. No. 17. Article 164.

Ganeeva V., Khrabrov K., Kadurin A., Tutubalina E.

The recent integration of natural language processing into chemistry has advanced drug discovery. Molecule representations in language models (LMs) are crucial to enhance chemical understanding. We explored the ability of models to match the same chemical structures despite their different representations. Recognizing the same substance in different representations is an important component of emulating the understanding of how chemistry works. We propose Augmented Molecular Retrieval (AMORE), a flexible zero-shot framework for the assessment of chemistry LMs of different natures. The framework is based on SMILES augmentations that maintain a foundational chemical structure. The proposed method facilitates the similarity between the embedding representations of the molecule, its SMILES variation, and that of another molecule. Experiments indicate that the tested ChemLLMs are still not robust to different SMILES representations. We evaluated the models on various tasks, including the molecular captioning on ChEBI-20 benchmark and classification and regression tasks of MoleculeNet benchmark. We show that the results’ change after SMILES strings variations align with the proposed AMORE framework.

Keywords: LLM

Publication based on the results of: Complex language and semantic models in artificial intelligence (2025)