{"about":{"site":"https://codewithpapers.app","non_affiliation":"Code with Papers and Syntology are not affiliated with, endorsed by, or sponsored by Papers with Code, Meta, or the pwc-archive mirror.","licence":"CC BY-SA 4.0","licence_url":"https://creativecommons.org/licenses/by-sa/4.0/legalcode","attribution":"https://codewithpapers.app/attribution","modified":"archive material modified by Syntology; see the attribution page"},"url":"/paper/reinforcement-learning-driven-linker-design","title":"Reinforcement Learning-Driven Linker Design via Fast Attention-based Point Cloud Alignment","arxiv_id":"2306.08166","date":"2023-06-13","proceeding":null,"authors":["Rebecca M. Neeser","Mehmet Akdel","Daniel Kovtun","Luca Naef"],"abstract":"Proteolysis-Targeting Chimeras (PROTACs) represent a novel class of small molecules which are designed to act as a bridge between an E3 ligase and a disease-relevant protein, thereby promoting its subsequent degradation. PROTACs are composed of two protein binding \"active\" domains, linked by a \"linker\" domain. The design of the linker domain is challenging due to geometric and chemical constraints given by its interactions, and the need to maximize drug-likeness. To tackle these challenges, we introduce ShapeLinker, a method for de novo design of linkers. It performs fragment-linking using reinforcement learning on an autoregressive SMILES generator. The method optimizes for a composite score combining relevant physicochemical properties and a novel, attention-based point cloud alignment score. This new method successfully generates linkers that satisfy both relevant 2D and 3D requirements, and achieves state-of-the-art results in producing novel linkers assuming a target linker conformation. This allows for more rational and efficient PROTAC design and optimization. Code and data are available at https://github.com/aivant/ShapeLinker.","url_abs":"https://arxiv.org/abs/2306.08166v1","url_pdf":"https://arxiv.org/pdf/2306.08166v1.pdf","source":{"archive":"pwc-archive (Hugging Face), CC BY-SA 4.0","snapshot":"2025-07-28","licence_url":"https://creativecommons.org/licenses/by-sa/4.0/legalcode","row_kind":"abstracts"},"code_links":[{"paper_slug":"reinforcement-learning-driven-linker-design","repo_url":"https://github.com/aivant/shapelinker","is_official":1,"mentioned_in_paper":1,"mentioned_in_github":1,"framework":"pytorch","reach":null}],"tasks":[{"task_slug":"reinforcement-learning-2","task_name":"reinforcement-learning"}],"methods":[],"datasets_introduced":[],"methods_introduced":[],"results":[],"syntology":{"atlas_url":null,"mcp":null,"developers":"https://syntology.ai/developers"},"arxiv_metadata":null,"syntology_extracted_results":null}