RetroRanker: leveraging reaction changes to improve retrosynthesis prediction through re-ranking

Abstract

Retrosynthesis is an important task in organic chemistry. Recently, numerous data-driven approaches have achieved promising results in this task. However, in practice, these data-driven methods might lead to sub-optimal outcomes by making predictions based on the training data distribution, a phenomenon we refer as frequency bias. For example, in template-based approaches, low-ranked predictions are typically generated by less common templates with low confidence scores which might be too low to be comparable, and it is observed that recorded reactants can be among these low-ranked predictions. In this work, we introduce RetroRanker, a ranking model built upon graph neural networks, designed to mitigate the frequency bias in predictions of existing retrosynthesis models through re-ranking. RetroRanker incorporates potential reaction changes of each set of predicted reactants in obtaining the given product to lower the rank of chemically unreasonable predictions. The predicted re-ranked results on publicly available retrosynthesis benchmarks demonstrate that we can achieve improvement on most state-of-the-art models with RetroRanker. Our preliminary studies also indicate that RetroRanker can enhance the performance of multi-step retrosynthesis.