EZSolver: Template-free prediction of polar enzymatic mechanisms via bidirectional flow matching and search
Abstract
Predicting enzymatic reaction mechanisms is critical for understanding enzyme function and for designing and dis-covering new enzymes. Current computational predictors rely on deterministic, rule-based dictionaries, which per-form well on in-distribution tasks but fail to generalize to out-of-distribution (OOD) chemistry. To address this limita-tion, we present EZSolver, a template-free, generative framework for polar enzymatic mechanism prediction. Powered by a flow matching predictor (EZFlow) and navigated by an evaluator-guided bidirectional beam search, EZSolver learns the chemistry of electron redistribution instead of memorizing rigid templates. Evaluated across diverse en-zyme classes, EZSolver achieves a 60.0% accuracy and an 84.6% chemical plausibility rate for full mechanism predic-tion of unseen polar enzymatic reactions. While rule-based models collapse without predefined templates, EZSolver successfully extrapolates chemical knowledge to infer uncatalogued pathways, as demonstrated during rigorous OOD benchmarking. By illuminating enzymatic chemical mechanisms, EZSolver helps pave the way for automated predic-tion of enzyme function and discovery and design of novel biocatalysts for sustainable chemistry.
Lifecycle
- biorxiv v1 2026-07-09 source ↗
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AI x Bio Discovery @aixbiobot.bsky.social · 787 followers neutral
EZSolver: Template-free prediction of polar enzymatic mechanisms via bidirectional flow matching and search [new] ...a generative framework that learns e- redistribution chemistry for accurate inference of uncatalogued pathways.
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bioRxiv Bioinfo @biorxiv-bioinfo.bsky.social · 4920 followers neutral
EZSolver: Template-free prediction of polar enzymatic mechanisms via bidirectional flow matching and search https://www.biorxiv.org/content/10.64898/2026.07.08.737313v1
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bioRxivpreprint @biorxivpreprint.bsky.social · 8895 followers neutral
EZSolver: Template-free prediction of polar enzymatic mechanisms via bidirectional flow matching and search https://www.biorxiv.org/content/10.64898/2026.07.08.737313v1