t-SMILES: A Scalable Fragment-based Molecular Representation Framework for De Novo Molecule Generation

Effective representation of molecules is a crucial factor affecting the performance of artificial intelligence models. This study introduces a flexible, fragment-based, multiscale molecular representation framework called t-SMILES (tree-based SMILES) with three code algorithms: TSSA (t-SMILES with Shared Atom), TSDY (t-SMILES with Dummy Atom) and TSID (t-SMILES with ID). It describes molecules using SMILES-type strings obtained by performing a breadth-first search on a full binary tree formed from a fragmented molecular graph. Systematic evaluations using JTVAE, BRICS, MMPA, and Scaffold show the feasibility to construct a multi-code molecular description system, where various descriptions complement each other, enhancing the overall performance. Additionally, it exhibits impressive performance on low-resource datasets, whether the model is original, data augmented, or pre-training fine-tuned. It significantly outperforms classical SMILES, DeepSMILES, SELFIES and baseline models in goal-directed tasks. Furthermore, it surpasses start-of-the-art fragment, graph and SMILES based approaches on ChEMBL, Zinc, and QM9.