DeCAF Framework Enables Fast All-Atom Protein Structure Prediction with Few Inference Steps
Researchers have introduced DeCAF (Denoiser Cofolding All-Atom Flowmap), a framework that distills state-of-the-art all-atom cofolding models into faster approximations requiring only a few inference steps. Current generative models for predicting 3D biomolecular structures are computationally expensive due to iterative diffusion rollouts. DeCAF significantly reduces computational cost while maintaining or improving accuracy, which could make protein-ligand structure prediction more practical for drug discovery and inference-time search.
Posted to arXiv on June 7, 2026, the DeCAF paper presents a method for compressing expensive diffusion-based cofolding models into flow maps that generate high-quality 3D biomolecular structures in far fewer function evaluations (NFEs). The framework is built on a denoiser-based formulation with endpoint losses supporting SE(3) rigid alignment, which the authors identify as critical for training accuracy. A change-of-variables technique allows DeCAF to operate within the sigma-space noise schedule of EDM-style architectures, enabling direct distillation from pretrained models without retraining from scratch. Applied to the Boltz-1x model, DeCAF-Boltz statistically outperforms its teacher on both RMSD accuracy and physical validity scores on the Runs N' Poses benchmark under strict NFE budgets, and shows a more favorable Pareto frontier on PoseBusters. When distilling the Pearl cofolding model, DeCAF-Pearl matches its teacher's success rate while using five times fewer NFEs. The authors also introduce a reward-guided inference-time search framework leveraging DeCAF's flowmap lookahead to further improve sampling quality. Code has been released publicly.
What's missing
The paper does not report wall-clock time benchmarks or hardware requirements, making it difficult to assess real-world deployment speedups beyond NFE counts. Generalization to biomolecular systems beyond protein-ligand complexes (e.g., RNA, DNA, or multi-protein assemblies) is not evaluated. Independent replication has not yet occurred given the preprint status.
What different sources said
- arXiv cs.LGCenter
Few-step Cofolding with All-Atom Flow Maps
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