Explainable Molecular Property Prediction: Aligning Chemical Concepts with Predictions via Language Models (2405.16041v3)

Abstract: Providing explainable molecular property predictions is critical for many scientific domains, such as drug discovery and material science. Though transformer-based LLMs have shown great potential in accurate molecular property prediction, they neither provide chemically meaningful explanations nor faithfully reveal the molecular structure-property relationships. In this work, we develop a framework for explainable molecular property prediction based on LLMs, dubbed as Lamole, which can provide chemical concepts-aligned explanations. We take a string-based molecular representation -- Group SELFIES -- as input tokens to pretrain and fine-tune our Lamole, as it provides chemically meaningful semantics. By disentangling the information flows of Lamole, we propose combining self-attention weights and gradients for better quantification of each chemically meaningful substructure's impact on the model's output. To make the explanations more faithfully respect the structure-property relationship, we then carefully craft a marginal loss to explicitly optimize the explanations to be able to align with the chemists' annotations. We bridge the manifold hypothesis with the elaborated marginal loss to prove that the loss can align the explanations with the tangent space of the data manifold, leading to concept-aligned explanations. Experimental results over six mutagenicity datasets and one hepatotoxicity dataset demonstrate Lamole can achieve comparable classification accuracy and boost the explanation accuracy by up to 14.3%, being the state-of-the-art in explainable molecular property prediction.