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Poster

Double-Ended Synthesis Planning with Goal-Constrained Bidirectional Search

Kevin Yu · Jihye Roh · Ziang Li · Wenhao Gao · Runzhong Wang · Connor Coley


Abstract: Computer-aided synthesis planning (CASP) algorithms have demonstrated expert-level abilities in planning retrosynthetic routes from purchasable building blocks. However, current search methods assume the sufficiency of reaching arbitrary building blocks, failing to address the common real-world constraint where using specific molecules is desired. To this end, we present a novel formulation of synthesis planning with starting material constraints. Under this formulation, we propose Double-Ended Synthesis Planning ($\texttt{DESP}$), a novel CASP algorithm under a _bidirectional graph search_ scheme that interleaves expansions from the target and from the goal starting materials to ensure constraint satisfiability. The search algorithm is guided by a goal-conditioned cost network learned offline from a partially observed hypergraph of valid chemical reactions. We demonstrate the utility of $\texttt{DESP}$ in improving solve rates and reducing the number of search expansions by biasing synthesis planning towards expert goals on multiple new benchmarks. $\texttt{DESP}$ can make use of existing one-step retrosynthesis models, and we anticipate its performance to scale as these one-step model capabilities improve.

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