RetroGEF: Dynamic Graph Edit Flow for Single-Step Retrosynthesis

Xiaozhuang Song, Xuemin Chen, Xinjian Zhao, Yaoyao Xu, Tianshu Yu

Retrosynthesis enables the discovery of viable synthetic routes to target molecules. It plays a central role in modern drug discovery and materials design. Retrosynthesis involves molecular graph transformations that can change both connectivity and graph size. These transformations may introduce reactant components absent from the target while revising the product-derived structure. To model these transformations, we propose RetroGEF, a flow-based generative model for single-step retrosynthesis. Starting from the target molecule, it constructs possible reactants by adding atoms and changing bonds in the molecular graph. RetroGEF models molecular transformations and changes in graph size within the same generative process, rather than relying on a fixed-size graph canvas. It learns this process directly from product--reactant pairs without requiring a prescribed edit order. Experiments on representative retrosynthesis benchmarks demonstrate that RetroGEF achieves state-of-the-art performance.