FLOWR: Flow Matching for Structure-Aware De Novo, Interaction- and Fragment-Based Ligand Generation
This work addresses the challenge of efficient and accurate ligand generation for drug design, offering a novel method with significant speed improvements, though it appears incremental as it builds on existing flow-based approaches.
The authors tackled the problem of generating and optimizing 3D ligands for drug discovery by introducing FLOWR, a structure-based framework that integrates flow matching and equivariant optimal transport, which achieved state-of-the-art performance in validity, accuracy, and interaction recovery with up to 70-fold faster inference speed.
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