ReactEmbed: A Cross-Domain Framework for Protein-Molecule Representation Learning via Biochemical Reaction Networks

Abstract

The challenge in computational biology and drug discovery lies in creating comprehensive representations of proteins and molecules that capture their intrinsic properties and interactions. Traditional methods often focus on unimodal data, such as protein sequences or molecular structures, limiting their ability to capture complex biochemical relationships. This work enhances these representations by integrating biochemical reactions encompassing interactions between molecules and proteins. By leveraging reaction data alongside pre-trained embeddings from state-of-the-art protein and molecule models, we develop ReactEmbed, a novel method that creates a unified embedding space through contrastive learning. We evaluate ReactEmbed across diverse tasks, including drug-target interaction, protein-protein interaction, protein property prediction, and molecular property prediction, consistently surpassing all current state-of-the-art models. Notably, we showcase ReactEmbed's practical utility through successful implementation in lipid nanoparticle-based drug delivery, enabling zero-shot prediction of blood-brain barrier permeability for protein-nanoparticle complexes. The code and comprehensive database of reaction pairs are available for open use at \href{https://github.com/amitaysicherman/ReactEmbed}{GitHub}.