PolyRetro: Few-shot Polymer Retrosynthesis via Domain Adaptation

Polymers appear everywhere in our daily lives -- fabrics, plastics, rubbers, etc. -- and we could hardly live without them. To make polymers, chemists develop processes that combine smaller building blocks~(monomers) to form long chains or complex networks~(polymers). These processes are called polymerizations and will usually take lots of human efforts to develop. Although machine learning models for small molecules have generated lots of promising results, the prediction problem for polymerization is new and suffers from the scarcity of polymerization datasets available in the field. Furthermore, the problem is made even more challenging by the large size of the polymers and the additional recursive constraints, which are not present in the small molecule problem. In this paper, we make an initial step towards this challenge and propose a learning-based search framework that can automatically identify a sequence of reactions that lead to the polymerization of a target polymer with minimal polymerization data involved. Our method transfers models trained on small molecule datasets for retrosynthesis to check the validity of polymerization reaction. Furthermore, our method also incorporates a template prior learned on a limited amount of polymer data into the framework to adapt the model from small molecule to the polymer domain. We demonstrate that our method is able to propose high-quality polymerization plans for a dataset of 52 real-world polymers, of which a significant portion successfully recovers the currently-in-used polymerization processes in the real world.