Efficient 3D Molecular Generation with Flow Matching and Scale Optimal Transport

Ross Irwin, Alessandro Tibo, Jon Paul Janet, Simon Olsson

Keywords: Generative AI, Molecular Generation, Flow Matching, Computational Chemistry, AI for Science

Abstract: Generative models for 3D drug design have gained prominence recently for their potential to design ligands directly within protein pockets. Current approaches, however, often suffer from very slow sampling times or generate molecules with poor chemical validity. Addressing these limitations, we propose Semla, a scalable E(3)-equivariant message passing architecture. We further introduce a molecular generation model, MolFlow, which is trained using flow matching along with scale optimal transport, a novel extension of equivariant optimal transport. Our model produces state-of-the-art results on benchmark datasets with just 100 sampling steps. Crucially, MolFlow samples high quality molecules with as few as 20 steps, corresponding to a two order-of-magnitude speed-up compared to state-of-the-art, without sacrificing performance. Furthermore, we highlight limitations of current evaluation methods for 3D generation and propose new benchmark metrics for unconditional molecular generators. Finally, using these new metrics, we compare our model's ability to generate high quality samples against current approaches and further demonstrate MolFlow's strong performance.

Submission Number: 31