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research article

FSscore: A Personalized Machine Learning-Based Synthetic Feasibility Score

Neeser, Rebecca M.  
•
Correia, Bruno  
•
Schwaller, Philippe  
November 1, 2024
Chemistry-Methods

Determining whether a molecule can be synthesized is crucial in chemistry and drug discovery, as it guides experimental prioritization and molecule ranking in de novo design tasks. Existing scoring approaches to assess synthetic feasibility struggle to extrapolate to new chemical spaces or fail to discriminate based on subtle differences such as chirality. This work addresses these limitations by introducing the Focused Synthesizability score (FSscore), which uses machine learning to rank structures based on their relative ease of synthesis. First, a baseline trained on an extensive set of reactant-product pairs is established, which is then refined with expert human feedback tailored to specific chemical spaces. This targeted fine-tuning improves performance on these chemical scopes, enabling more accurate differentiation between molecules that are hard and easy to synthesize. The FSscore showcases how a human-in-the-loop framework can be utilized to optimize the assessment of synthetic feasibility for various chemical applications.

  • Details
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Type
research article
DOI
10.1002/cmtd.202400024
Scopus ID

2-s2.0-85206563399

Author(s)
Neeser, Rebecca M.  

École Polytechnique Fédérale de Lausanne

Correia, Bruno  

École Polytechnique Fédérale de Lausanne

Schwaller, Philippe  

École Polytechnique Fédérale de Lausanne

Date Issued

2024-11-01

Published in
Chemistry-Methods
Volume

4

Issue

11

Article Number

e202400024

Subjects

cheminformatics

•

de novodesign

•

machine learning

•

synthesizability

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
LIAC  
LPDI  
FunderFunding(s)Grant NumberGrant URL

Swiss National Science Foundation

NCCR Catalysis

180544

Available on Infoscience
January 25, 2025
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/244001
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