VQ-Atom: Semantic Discretization of Local Atomic Environments for Molecular Representation Learning

Abstract

Large language models succeed by combining large-scale pretraining with meaningful discrete tokens. In molecular machine learning, SMILES is widely used as a token representation, but it is primarily a linearization format for molecular graphs rather than a semantic decomposition of chemistry. We propose VQ-Atom, a semantic tokenization framework that assigns discrete atom-level tokens based on local chemical environments via vector quantization. Unlike SMILES tokens, VQ-Atom tokens encode graph-local chemical context and are aligned with molecular structure. On protein-cold drug--target interaction prediction using the KIBA dataset, VQ-Atom substantially improves global ranking performance, achieving AUROC of 0.79 while substantially outperforming both SMILES-based and continuous molecular representations under an identical downstream architecture. Furthermore, VQ-Atom enables approximately 3 times faster downstream training than continuous atom-level representations by replacing per-atom continuous features with reusable discrete tokens. These results suggest that molecular tokenization is not merely a preprocessing step, but a central design choice. In particular, well-structured tokens can encode substantial chemical semantics, reducing the burden on downstream learning. VQ-Atom can be interpreted as defining a molecular language, where tokens correspond to chemically meaningful atomic environments, suggesting that token design may constitute an additional axis of machine learning research alongside architecture, objectives, and optimization.