Link-INVENT: Generative Linker Design with Reinforcement Learning

Jeff Guo, Franziska Knuth, Christian Margreitter, Jon Paul Janet, Kostas Papadopoulos, Ola Engkvist, Atanas Patronov

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.