Retrosynthesis Prediction via Search in (Hyper) Graph
This work addresses a specific limitation in retrosynthesis prediction for chemists, offering an incremental improvement over existing methods.
The authors tackled the problem of retrosynthesis prediction for complex organic reactions, proposing RetroSiG, a semi-template-based method that uses search in molecular and hypergraphs to handle multiple reaction centers and shared leaving groups, achieving competitive results.
Predicting reactants from a specified core product stands as a fundamental challenge within organic synthesis, termed retrosynthesis prediction. Recently, semi-template-based methods and graph-edits-based methods have achieved good performance in terms of both interpretability and accuracy. However, due to their mechanisms these methods cannot predict complex reactions, e.g., reactions with multiple reaction center or attaching the same leaving group to more than one atom. In this study we propose a semi-template-based method, the \textbf{Retro}synthesis via \textbf{S}earch \textbf{i}n (Hyper) \textbf{G}raph (RetroSiG) framework to alleviate these limitations. In the proposed method, we turn the reaction center identification and the leaving group completion tasks as tasks of searching in the product molecular graph and leaving group hypergraph respectively. As a semi-template-based method RetroSiG has several advantages. First, RetroSiG is able to handle the complex reactions mentioned above by its novel search mechanism. Second, RetroSiG naturally exploits the hypergraph to model the implicit dependencies between leaving groups. Third, RetroSiG makes full use of the prior, i.e., one-hop constraint. It reduces the search space and enhances overall performance. Comprehensive experiments demonstrated that RetroSiG achieved competitive results. Furthermore, we conducted experiments to show the capability of RetroSiG in predicting complex reactions. Ablation experiments verified the efficacy of specific elements, such as the one-hop constraint and the leaving group hypergraph.