The ModelSEED Biochemistry Database, 2026 update: grading multi-source thermodynamics

Abstract

Abstract The ModelSEED Biochemistry Database ( https://modelseed.org/biochem ) supplies foundational mass- and charge-balanced reaction networks for metabolic reconstructions. Here we present an update on the biochemistry where the database has been expanded to ∼ 46,000 compounds, featuring ∼ 37,000 metabolic structures, and ∼ 48,000 reactions. We expanded our approach for handling thermodynamic data, enabling multiple sources of data to be derived, integrated, and presented to the wider research community. We now publish predictions of pKa, reaction energy (and respective uncertainties), and estimates of reaction direction from multiple independent sources. Reaction directions are graded gold, silver, or bronze according to the strength of supporting evidence, which is complemented by the prediction from an ensemble of large language models. These diverse sources empower users to understand agreements or discrepancies in directionality for ∼27,000 reactions. Finally, to ensure data integrity, a new conflict-resolution pipeline reconciles structures across sources, documenting input from curators. Our work is publicly available at https://github.com/ModelSEED/ModelSEEDDatabase .