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PreprintCited by 102Computational Drug Discovery MethodsProtein Degradation and InhibitorsChemical Synthesis and Analysis

Link-INVENT: Generative Linker Design with Reinforcement Learning

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Guo, Jeff, Knuth, Franziska, Margreitter, Christian, Janet, Jon Paul, Papadopoulos, Kostas, Engkvist, Ola, Patronov, Atanas·2022·Digital Discovery
DOI 10.26434/chemrxiv-2022-qkx9f
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Abstract

In this work, we present Link-INVENT as an extension to the existing de novo molecular design platform REINVENT. We provide illustrative examples on how Link-INVENT can be applied on fragment linking, scaffold hopping, and PROTACs design case studies where the desirable molecules should satisfy a combination of different criteria. With the help of Reinforcement Learning, the agent used by Link-INVENT learns to generate favourable linkers connecting molecular subunits that satisfy diverse objectives, facilitating practical application of the model for real-world drug discovery projects. We also introduce a range of linker-specific objectives in the scoring function of REINVENT. The code is freely available at https://github.com/MolecularAI/Reinvent.

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Authors
Guo, J., Knuth, F., Margreitter, C., Janet, J. P., Papadopoulos, K., Engkvist, O., & Patronov, A.
Affiliations
  • AstraZeneca (Sweden) (SE)
  • Norwegian University of Science and Technology (NO)
Corresponding author
Patronov, Atanas
ORCID
Venue
Digital Discovery
Publisher
American Chemical Society (ACS)
Published
2022-04-24
Volume
2
Issue
2
Pages
392-408
ISSN
2635-098X (ISSN-L)
DOI
10.26434/chemrxiv-2022-qkx9f
OpenAlex
W4319164354
Cited by
101
References
62
Citations by year
2026: 30 · 2025: 29 · 2024: 26 · 2023: 15 · 2022: 1
FWCI
14.46
Type
journal article
Language
en
Open access
Licence
Locations
  • Digital Discovery (publishedVersion, cc-by)
  • ChemRxiv (acceptedVersion, cc-by)
  • Chalmers Research (Chalmers University of Technology) (submittedVersion)
Topics
  • Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chemical Synthesis and Analysis
Keywords
PROTACs, linker design, fragment linking, scaffold hopping, generative design, reinforcement learning

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