Multi-domain Distribution Learning for De Novo Drug Design

• URL: http://arxiv.org/abs/2508.17815v1
• Date: Mon, 25 Aug 2025 09:12:01 GMT
• Title: Multi-domain Distribution Learning for De Novo Drug Design
• Authors: Arne Schneuing, Ilia Igashov, Adrian W. Dobbelstein, Thomas Castiglione, Michael Bronstein, Bruno Correia,
• Abstract summary: DrugFlow is a generative model for structure-based drug design that integrates continuous flow matching with discrete Markov bridges.<n>We endow DrugFlow with an uncertainty estimate that is able to detect out-of-distribution samples.<n>We extend our model to also explore the conformational landscape of the protein by jointly sampling side chain angles and molecules.
• Score: 5.947157646283629
• License: http://creativecommons.org/licenses/by-sa/4.0/
• Abstract: We introduce DrugFlow, a generative model for structure-based drug design that integrates continuous flow matching with discrete Markov bridges, demonstrating state-of-the-art performance in learning chemical, geometric, and physical aspects of three-dimensional protein-ligand data. We endow DrugFlow with an uncertainty estimate that is able to detect out-of-distribution samples. To further enhance the sampling process towards distribution regions with desirable metric values, we propose a joint preference alignment scheme applicable to both flow matching and Markov bridge frameworks. Furthermore, we extend our model to also explore the conformational landscape of the protein by jointly sampling side chain angles and molecules.

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