Finding Pathways in Reaction Networks Guided by Energy Barriers Using Integer Linear Programing

Adittya Pal; Rolf Fagerberg; Jakob Lykke Andersen; Peter Dittrich; Daniel Merkle

doi:10.1002/minf.70021

journal article Mar 01, 2026

Finding Pathways in Reaction Networks Guided by Energy Barriers Using Integer Linear Programing

Adittya Pal

Rolf Fagerberg Jakob Lykke Andersen Peter Dittrich Daniel Merkle

Molecular Informatics Vol. 45 No. 3 · Wiley

View at Publisher Save 10.1002/minf.70021

Abstract

Analyzing synthesis pathways for target molecules in a chemical reaction network annotated with information on the kinetics of individual reactions is an area of active study. This work presents a computational methodology for searching for pathways in reaction networks which is based on integer linear programing and the modeling of reaction networks by directed hypergraphs. Often multiple pathways fit the given search criteria. To rank them, we develop an objective function based on physical arguments maximizing the probability of the pathway. We furthermore develop an automated pipeline to estimate the energy barriers of individual reactions in reaction networks. Combined, the methodology facilitates flexible and kinetically informed pathway investigations on large reaction networks by computational means, even for networks coming without kinetic annotation, such as those created via generative approaches for expanding molecular spaces. To demonstrate the methodology, we apply it on a chemical reaction network generated from 2‐hydroxyethanenitrile, water, and ammonia, where we search for pathways to glycine and 2‐hydroxyethanoic acid using the input molecules as precursors.

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Details

Published: Mar 01, 2026
Vol/Issue: 45(3)
License: View

Authors

A

Adittya Pal

Department of Mathematics and Computer Science University of Southern Denmark Odense Denmark

R

Rolf Fagerberg

Department of Mathematics and Computer Science University of Southern Denmark Odense Denmark

J

Jakob Lykke Andersen

Department of Mathematics and Computer Science University of Southern Denmark Odense Denmark

P

Peter Dittrich

Department of Mathematics and Computer Science Friedrich Schiller University Jena Jena Germany

D

Daniel Merkle

Department of Mathematics and Computer Science University of Southern Denmark Odense Denmark; Faculty of Technology Bielefeld University Bielefeld Germany

Cite This Article

Adittya Pal, Rolf Fagerberg, Jakob Lykke Andersen, et al. (2026). Finding Pathways in Reaction Networks Guided by Energy Barriers Using Integer Linear Programing. Molecular Informatics, 45(3). https://doi.org/10.1002/minf.70021

Finding Pathways in Reaction Networks Guided by Energy Barriers Using Integer Linear Programing

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