One of the key challenges in automated synthesis planning is to generate diverse and reliable chemical reactions. Many reactions can be naturally represented using graph transformation rules referred broadly to as reaction templates. Using reaction templates enables accurate and interpretable predictions but can suffer from limited coverage of the reaction space. On the other hand, template-free methods can increase the coverage but can be prone to making trivial mistakes and are challenging to interpret. A promising idea for constructing more interpretable template-free models is to model a reaction as a sequence of graph edits of the substrates. We extend this idea to retrosynthesis and scale it up to large datasets. We propose Molecule Edit Graph Attention Network (MEGAN), a template-free neural model that encodes reaction as a sequence of graph edits. We achieve competitive performance on both retrosynthesis and forward synthesis and in particular state-of-the-art top-k accuracy for larger K values. Crucially, the latter shows excellent coverage of the reaction space of our model. In summary, MEGAN brings together the strong elements of template-free and template-based models and can be applied to both retro and forward synthesis tasks.
Speakers: Mikołaj Sacha, Mikołaj Błaż, Piotr Byrski, Paweł Włodarczyk-Pruszyński, Stanisław Jastrzębski