Automatic Prediction of Molecular Properties Using Substructure Vector Embeddings within a Feature Selection Workflow

J Chem Inf Model. 2024 Dec 23. doi: 10.1021/acs.jcim.4c01862. Online ahead of print.

Abstract

Machine learning (ML) methods provide a pathway to accurately predict molecular properties, leveraging patterns derived from structure-property relationships within materials databases. This approach holds significant importance in drug discovery and materials design, where the rapid, efficient screening of molecules can accelerate the development of new pharmaceuticals and chemical materials for highly specialized target application. Unsupervised and self-supervised learning methods applied to graph-based or geometric models have garnered considerable traction. More recently, transformer-based language models have emerged as powerful tools. Nevertheless, their application entails considerable computational resources, owing to the need for an extensive pretraining process on a vast corpus of unlabeled chemical data sets. To this end, we present a semisupervised strategy that harnesses substructure vector embeddings in conjunction with a ML-based feature selection workflow to predict various molecular and drug properties. We evaluate the efficacy of our modeling methodology across a diverse range of data sets, encompassing both regression and classification tasks. Our findings demonstrate superior performance compared to most existing state-of-the-art algorithms, while offering advantages in terms of balancing model accuracy with computational requirements. Moreover, our approach provides deeper insights into feature interactions that are essential for model interpretability. A case study is conducted to predict the lipophilicity of chemical molecules, exemplifying the robustness of our strategy. The result underscores the importance of meticulous feature analysis and selection over a mere reliance on predictive modeling with a high degree of algorithmic complexity.