Prediction of blood–brain barrier and Caco-2 permeability through the Enalos Cloud Platform: combining contrastive learning and atom-attention message passing neural networks

In this study, we introduce a novel approach for predicting two key drug properties, blood-brain barrier (BBB) permeability and human intestinal absorption via Caco-2 permeability. Our methodology centers around a specialized neural network, the atom transformer-based Message Passing Neural Network (MPNN), which we have combined with contrastive learning techniques to enhance the process of representing and embedding molecular structures for more accurate property prediction. These innovative models focus on predicting BBB and Caco-2 permeability -two critical factors in drug absorption and distribution- which fall under the broader scope of ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties. The models are readily accessible online through the Enalos Cloud Platform which offers a user-friendly, AI-powered, ready-to-use web service that significantly streamlines the drug design process, enabling users to easily predict and understand the behavior of potential drug compounds within the human body.Scientific Contribution Our study combines an atom-attention Message Passing Neural Network (AA-MPNN) with contrastive learning (CL), which significantly improves predictive accuracy. Our model leverages self-supervised learning to expand the chemical space used in training and self-attention mechanisms to focus on critical molecular features, enhancing both model accuracy and interpretability. Additionally, the ready-to-use web service based on our model democratizes access to predictive tools for the scientific and regulatory communities.