Bridging Chemists and AI: An Expert-Augmented Framework for Interpretable Route Evaluation

Yujia Guo; Mikhail Kabeshov; Tat Hong Duong Le; Samuel Genheden; Marco V. Mijangos; Varvara Voinarvoska; Giulia Bergonzini; Ola Engkvist; Samuel Kaski

arXiv · 2605.29108

Bridging Chemists and AI: An Expert-Augmented Framework for Interpretable Route Evaluation

Yujia Guo·Mikhail Kabeshov·Tat Hong Duong Le·Samuel Genheden·Marco V. Mijangos·Varvara Voinarvoska·Giulia Bergonzini·Ola Engkvist·Samuel Kaski

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Abstract

Selecting efficient multi-step synthetic routes is a central challenge in organic synthesis, particularly in medicinal and process chemistry, where route choice directly impacts feasibility, cost, and development efficiency. Data-driven assessment systems often oversimplify the multi-objective nature of synthesis design and rely on proxy datasets, such as patent routes, rather than universally grounded criteria. To address this, we introduce an expert-augmented, data-driven scoring framework that integrates machine learning with chemists' domain knowledge for both numerical and explainable route assessment. A DeepSets-based model is trained using tree edit distance between reference and machine-generated routes, and then fine-tuned with expert evaluations to produce both quantitative scores and interpretable qualitative categories: Good, Plausible, and Bad. The resulting system achieves a Spearman correlation coefficient of 0.78 and a Pearson correlation of 0.77 for category assessment prediction, and 60.2% top-1 ranking accuracy for score prediction, substantially outperforming the previous baseline of 17.5%.

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Yujia Guo, Mikhail Kabeshov, Tat Hong Duong Le, Samuel Genheden, Marco V. Mijangos, Varvara Voinarvoska, Giulia Bergonzini, Ola Engkvist, Samuel Kaski. 2026-05-27. Bridging Chemists and AI: An Expert-Augmented Framework for Interpretable Route Evaluation. https://arxiv.org/abs/2605.29108

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