Identifying Structure-Property Relationships through SMILES Syntax Analysis with Self-Attention Mechanism

Abstract

Recognizing substructures and their relations embedded in a molecular structure representation is a key process for structure–activity or structure–property relationship (SAR/SPR) studies. A molecular structure can be explicitly represented as either a connection table (CT) or linear notation, such as SMILES, which is a language describing the connectivity of atoms in the molecular structure. Conventional SAR/SPR approaches rely on partitioning the CT into a set of predefined substructures as structural descriptors. In this work, we propose a new method to identifying SAR/SPR through linear notation (for example, SMILES) syntax analysis with self-attention mechanism, an interpretable deep learning architecture. The method has been evaluated by predicting chemical properties, toxicology, and bioactivity from experimental data sets. Our results demonstrate that the method yields superior performance compared with state-of-the-art models. Moreover, the method can produce chemically interpretable results, which can be used for a chemist to design and synthesize the activity- or property-improved compounds.