A 3D-Shape Similarity-based Contrastive Approach to Molecular Representation Learning

Austin Atsango, Nathaniel Lee Diamant, Ziqing Lu, Tommaso Biancalani, Gabriele Scalia, Kangway V Chuang

Keywords: graph neural networks, representation learning, three-dimensional representations, conformers, shape similarity

Abstract: Molecular shape and geometry dictate key biophysical recognition processes, yet many modern graph neural networks disregard 3D information for molecular property prediction. Here, we propose a new contrastive-learning procedure for graph neural networks, Molecular Contrastive Learning from Shape Similarity (MolCLaSS), that implicitly learns a three-dimensional representation. Rather than directly encoding or targeting three-dimensional poses, MolCLaSS matches a similarity objective based on Gaussian overlays to learn a meaningful representation of molecular shape. We demonstrate how this framework naturally captures key aspects of three-dimensionality that two-dimensional representations cannot and provides an inductive framework for scaffold hopping.