Synthetic accessibility prediction is a task to estimate how easily a given molecule might be synthesizable in the laboratory, playing a crucial role in computer-aided molecular design. Although synthesis planning programs can determine synthesis routes, their slow processing times make them impractical for large-scale molecule screening. On the other hand, existing rapid synthesis accessibility estimation methods offer speed but typically lack integration with actual synthesis routes and building block information. In this work, we introduce BR-SAScore, an enhanced version of SAScore that integrates the available building block information (B) and reaction knowledge (R) from synthesis planning programs into the scoring process. In particular, we differentiate fragments inherent in building blocks and fragments to be derived from synthesis (reactions) when scoring synthetic accessibility. Compared to existing methods, our experimental findings demonstrate that BR-SAScore offers more accurate and precise identification of a molecule's synthetic accessibility by the synthesis planning program with a fast calculation time. Moreover, we illustrate how BR-SAScore provides chemically interpretable results, aligning with the capability of the synthesis planning program embedded with the same reaction knowledge and available building blocks. Scientific contribution We introduce BR-SAScore, an extension of SAScore, to estimate the synthetic accessibility of molecules by leveraging known building-block and reactivity information. In our experiments, BR-SAScore shows superior prediction performance on predicting molecule synthetic accessibility compared to previous methods, including SAScore and deep-learning models, while requiring significantly less computation time. In addition, we show that BR-SAScore is able to precisely identify the chemical fragment contributing to the synthetic infeasibility, holding great potential for future molecule synthesizability optimization.

中文翻译：

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使用构建块和反应感知 SAScore 估计分子的合成可及性


合成可及性预测是一项估计给定分子在实验室合成难易程度的任务，在计算机辅助分子设计中发挥着至关重要的作用。尽管合成规划程序可以确定合成路线，但其缓慢的处理时间使得它们对于大规模分子筛选来说不切实际。另一方面，现有的快速合成可达性估计方法提供了速度，但通常缺乏与实际合成路线和构建块信息的集成。在这项工作中，我们引入了 BR-SAScore，这是 SAScore 的增强版本，它将合成规划程序中的可用构建块信息 (B) 和反应知识 (R) 集成到评分过程中。特别是，在对合成可访问性进行评分时，我们区分构建块中固有的片段和从合成（反应）衍生的片段。与现有方法相比，我们的实验结果表明，BR-SAScore 通过合成规划程序和快速计算时间提供了更准确和精确的分子合成可及性识别。此外，我们还说明了 BR-SAScore 如何提供化学上可解释的结果，与嵌入相同反应知识和可用构建模块的合成规划程序的功能保持一致。科学贡献 我们引入了 BR-SAScore（SAScore 的扩展），通过利用已知的构建模块和反应性信息来估计分子的合成可及性。在我们的实验中，与之前的方法（包括 SAScore 和深度学习模型）相比，BR-SAScore 在预测分子合成可及性方面表现出卓越的预测性能，同时需要的计算时间显着减少。 此外，我们还表明 BR-SAScore 能够精确识别导致合成不可行性的化学片段，为未来分子合成性优化带来巨大潜力。