FLOWR: Flow Matching for Structure-Aware De Novo, Interaction- and Fragment-Based Ligand Generation

We introduce FLOWR, a novel structure-based framework for the generation and optimization of three-dimensional ligands. FLOWR integrates continuous and categorical flow matching with equivariant optimal transport, enhanced by an efficient protein pocket conditioning. Alongside FLOWR, we present SPINDR, a thoroughly curated dataset comprising ligand-pocket co-crystal complexes specifically designed to address existing data quality issues. Empirical evaluations demonstrate that FLOWR surpasses current state-of-the-art diffusion- and flow-based methods in terms of PoseBusters-validity, pose accuracy, and interaction recovery, while offering a significant inference speedup, achieving up to 70-fold faster performance. In addition, we introduce FLOWR:multi, a highly accurate multi-purpose model allowing for the targeted sampling of novel ligands that adhere to predefined interaction profiles and chemical substructures for fragment-based design without the need of re-training or any re-sampling strategies

@article{cremer2025_2504.10564,
  title={ FLOWR: Flow Matching for Structure-Aware De Novo, Interaction- and Fragment-Based Ligand Generation },
  author={ Julian Cremer and Ross Irwin and Alessandro Tibo and Jon Paul Janet and Simon Olsson and Djork-Arné Clevert },
  journal={arXiv preprint arXiv:2504.10564},
  year={ 2025 }
}