TSIS: A Supplementary Algorithm to t-SMILES for Fragment-based Molecular Representation

String-based molecular representations, such as SMILES, are a de facto standard for linearly representing molecular information. However, the must be paired symbols and the parsing algorithm result in long grammatical dependencies, making it difficult for even state-of-the-art deep learning models to accurately comprehend the syntax and semantics. Although DeepSMILES and SELFIES have addressed certain limitations, they still struggle with advanced grammar, which makes some strings difficult to read. This study introduces a supplementary algorithm, TSIS (TSID Simplified), to t-SMILES family. Comparative experiments between TSIS and another fragment-based linear solution, SAFE, indicate that SAFE presents challenges in managing long-term dependencies in grammar. TSIS continues to use the tree defined in t-SMILES as its foundational data structure, which sets it apart from the SAFE model. The performance of TSIS models surpasses that of SAFE models, indicating that the tree structure of the t-SMILES family provides certain advantages.

Fragment-based t-SMILES for de novo molecular generation

At present, sequence-based and graph-based models are two of popular used molecular generative models. In this study, we introduce a general-purposed, fragment-based, hierarchical molecular representation named t-SMILES (tree-based SMILES) which describes molecules using a SMILES-type string obtained by doing breadth first search (BFS) on full binary molecular tree formed from fragmented molecular graph. The proposed t-SMILES combines the advantages of graph model paying more attention to molecular topology structure and language model possessing powerful learning ability. Experiments with feature tree rooted JTVAE and chemical reaction-based BRICS molecular decomposing algorithms using sequence-based autoregressive generation models on three popular molecule datasets including Zinc, QM9 and ChEMBL datasets indicate that t-SMILES based models significantly outperform previously proposed fragment-based models and being competitive with classical SMILES based and graph-based approaches. Most importantly, we proposed a new perspective for fragment based molecular designing. Hence, SOTA powerful sequence-based solutions could be easily applied for fragment based molecular tasks.