mlsanityData to 7 Oct 2026

DecompDiff: Diffusion Models with Decomposed Priors for Structure-Based Drug Design

arXiv 2403.07902 ↗First posted 26 Feb 2024q-bio.BM cs.LGcited by 87

On the map: Diffusion models → Flow matching, time series and science

Abstract (arXiv)

Designing 3D ligands within a target binding site is a fundamental task in drug discovery. Existing structured-based drug design methods treat all ligand atoms equally, which ignores different roles of atoms in the ligand for drug design and can be less efficient for exploring the large drug-like molecule space. In this paper, inspired by the convention in pharmaceutical practice, we decompose the ligand molecule into two parts, namely arms and scaffold, and propose a new diffusion model, DecompDiff, with decomposed priors over arms and scaffold. In order to facilitate the decomposed generation and improve the properties of the generated molecules, we incorporate both bond diffusion in the model and additional validity guidance in the sampling phase. Extensive experiments on CrossDocked2020 show that our approach achieves state-of-the-art performance in generating high-affinity molecules while maintaining proper molecular properties and conformational stability, with up to -8.39 Avg. Vina Dock score and 24.5 Success Rate. The code is provided at https://github.com/bytedance/DecompDiff

Key facts. Cited by 87 papers in the map (data through 7 Oct 2026). Placed in Flow matching, time series and science, one of 14 directions in Diffusion models. Builds on 35 of its 68 references that are in the map. First posted on arXiv 26 Feb 2024.

Builds on

35 of 68 references.

Closest ancestors · 5

Same direction, newest first

  1. 2022Structure-based Drug Design with Equivariant Diffusion Models24 Oct
  2. 2022Equivariant 3D-Conditional Diffusion Models for Molecular Linker Design11 Oct
  3. 2022DiGress: Discrete Denoising diffusion for graph generation29 Sep
  4. 2022Equivariant Diffusion for Molecule Generation in 3D31 Mar
  5. 2022GeoDiff: a Geometric Diffusion Model for Molecular Conformation Generation6 Mar

Other references · 30

  1. 2014Adam: A Method for Stochastic Optimizationcited by 36,960
  2. 2020Denoising Diffusion Probabilistic Modelscited by 20,851
  3. 2021Diffusion Models Beat GANs on Image Synthesiscited by 8,185
  4. 2015Deep Unsupervised Learning using Nonequilibrium Thermodynamicscited by 7,005
  5. 2022Hierarchical Text-Conditional Image Generation with CLIP Latentscited by 6,539
  6. 2022Classifier-Free Diffusion Guidancecited by 5,717
  7. 2019Generative Modeling by Estimating Gradients of the Data Distributioncited by 4,067
  8. 2021Improved Denoising Diffusion Probabilistic Modelscited by 3,736
  9. 2021GLIDE: Towards Photorealistic Image Generation and Editing with Text-Guided Diffusion Modelscited by 3,595
  10. 2020DiffWave: A Versatile Diffusion Model for Audio Synthesiscited by 1,339
  11. 2022Diffusion-LM Improves Controllable Text Generationcited by 1,006
  12. 2021E(n) Equivariant Graph Neural Networkscited by 951
18 more
  1. 2018Tensor field networks: Rotation- and translation-equivariant neural networks for 3D point cloudscited by 735
  2. 2020SE(3)-Transformers: 3D Roto-Translation Equivariant Attention Networkscited by 602
  3. 2021Argmax Flows and Multinomial Diffusion: Learning Categorical Distributionscited by 566
  4. 2020Directional Message Passing for Molecular Graphscited by 556
  5. 2019Analyzing Learned Molecular Representations for Property Predictioncited by 373
  6. 2022Pocket2Mol: Efficient Molecular Sampling Based on 3D Protein Pocketscited by 182
  7. 20233D Equivariant Diffusion for Target-Aware Molecule Generation and Affinity Predictioncited by 176
  8. 2022A 3D Generative Model for Structure-Based Drug Designcited by 148
  9. 2021MARS: Markov Molecular Sampling for Multi-objective Drug Discoverycited by 125
  10. 2022Generating 3D Molecules for Target Protein Bindingcited by 104
  11. 2021Independent SE(3)-Equivariant Models for End-to-End Rigid Protein Dockingcited by 81
  12. 2021Generating 3D Molecules Conditional on Receptor Binding Sites with Deep Generative Modelscited by 72
  13. 2022DiffBP: Generative Diffusion of 3D Molecules for Target Protein Bindingcited by 58
  14. 2021Learning to design drug-like molecules in three-dimensional space using deep generative modelscited by 37
  15. 20223DLinker: An E(3) Equivariant Variational Autoencoder for Molecular Linker Designcited by 33
  16. 2022Zero-Shot 3D Drug Design by Sketching and Generatingcited by 24
  17. 2022Equivariant Shape-Conditioned Generation of 3D Molecules for Ligand-Based Drug Designcited by 19
  18. 2019DeepScaffold: a comprehensive tool for scaffold-based de novo drug discovery using deep learningcited by 15

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Cited by year (2026 to 7 Oct)

Citing papers per year: 2024: 32; 2025: 32; 2026: 23.

87 papers.

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  1. 2024MolCRAFT: Structure-Based Drug Design in Continuous Parameter Spacecited by 48
  2. 2024On Statistical Rates and Provably Efficient Criteria of Latent Diffusion Transformers (DiTs)cited by 39
  3. 2024Efficient Diffusion Models: A Comprehensive Survey from Principles to Practicescited by 39
  4. 2025Efficient Diffusion Models: A Surveycited by 35
  5. 2024On the Challenges and Opportunities in Generative AIcited by 31
  6. 2024DecompOpt: Controllable and Decomposed Diffusion Models for Structure-based Molecular Optimizationcited by 27
  7. 2024Diffusion Models in textitDe Novo Drug Designcited by 26
  8. 2024Aligning Target-Aware Molecule Diffusion Models with Exact Energy Optimizationcited by 25
  9. 2025LIDDIA: Language-based Intelligent Drug Discovery Agentcited by 24
  10. 2024Generative Flows on Synthetic Pathway for Drug Designcited by 20
  11. 2025PharmAgents: Building a Virtual Pharma with Large Language Model Agentscited by 20
  12. 2024CBGBench: Fill in the Blank of Protein-Molecule Complex Binding Graphcited by 19
38 more
  1. 2024Structure-based drug design by denoising voxel gridscited by 18
  2. 2025Multi-domain Distribution Learning for De Novo Drug Designcited by 15
  3. 2024Unified Convergence Analysis for Score-Based Diffusion Models with Deterministic Samplerscited by 14
  4. 2024TAGMol: Target-Aware Gradient-guided Molecule Generationcited by 12
  5. 2024Context-Guided Diffusion for Out-of-Distribution Molecular and Protein Designcited by 11
  6. 2025UniMoMo: Unified Generative Modeling of 3D Molecules for De Novo Binder Designcited by 11
  7. 2025Generating 3D Binding Molecules Using Shape-Conditioned Diffusion Models with Guidancecited by 10
  8. 2024Rethinking Specificity in SBDD: Leveraging Delta Score and Energy-Guided Diffusioncited by 9
  9. 2024Flow Matching for Accelerated Simulation of Atomic Transport in Crystalline Materialscited by 9
  10. 2024DiffGAD: A Diffusion-based Unsupervised Graph Anomaly Detectorcited by 9
  11. 2024Hotspot-Driven Peptide Design via Multi-Fragment Autoregressive Extensioncited by 9
  12. 2024Decomposed Direct Preference Optimization for Structure-Based Drug Designcited by 7
  13. 2025Unified Guidance for Geometry-Conditioned Molecular Generationcited by 7
  14. 2024Empower Structure-Based Molecule Optimization with Gradient Guided Bayesian Flow Networkscited by 6
  15. 2025Compositional Flows for 3D Molecule and Synthesis Pathway Co-designcited by 6
  16. 2025Piloting Structure-Based Drug Design via Modality-Specific Optimal Schedulecited by 6
  17. 2025Prior-Guided Flow Matching for Target-Aware Molecule Design with Learnable Atom Numbercited by 6
  18. 2024General Binding Affinity Guidance for Diffusion Models in Structure-Based Drug Designcited by 5
  19. 2024Evaluating Molecule Synthesizability via Retrosynthetic Planning and Reaction Predictioncited by 5
  20. 2025Graph-structured Small Molecule Drug Discovery Through Deep Learning: Progress, Challenges, and Opportunitiescited by 5
  21. 20253DMolFormer: A Dual-channel Framework for Structure-based Drug Discoverycited by 4
  22. 2024TurboHopp: Accelerated Molecule Scaffold Hopping with Consistency Modelscited by 3
  23. 2024Rectified Flow For Structure Based Drug Designcited by 3
  24. 2025BoKDiff: Best-of-K Diffusion Alignment for Target-Specific 3D Molecule Generationcited by 3
  25. 2025FROGENT: An End-to-End Full-process Drug Design Multi-Agent Systemcited by 3
  26. 2024AUTODIFF: Autoregressive Diffusion Modeling for Structure-based Drug Designcited by 2
  27. 2024Equivariant Blurring Diffusion for Hierarchical Molecular Conformer Generationcited by 2
  28. 2025Integrating Protein Dynamics into Structure-Based Drug Design via Full-Atom Stochastic Flowscited by 2
  29. 2025Controllable 3D Molecular Generation for Structure-Based Drug Design Through Bayesian Flow Networks and Gradient Integrationcited by 2
  30. 2025MolChord: Structure-Sequence Alignment for Protein-Guided Drug Designcited by 2
  31. 2025Unified all-atom molecule generation with neural fieldscited by 2
  32. 2026CAGenMol: Condition-Aware Diffusion Language Model for Goal-Directed Molecular Generationcited by 2
  33. 2026ToolMol: Evolutionary Agentic Framework for Multi-objective Drug Discoverycited by 2
  34. 2026Are we really tilting? The mechanics of reward guidance in flow and diffusion modelscited by 2
  35. 2026Speaking the Language of Science: Toward a General-Purpose Generative Foundation Model for the Natural Sciencescited by 2
  36. 2024From Theory to Therapy: Reframing SBDD Model Evaluation via Practical Metricscited by 1
  37. 2024Task-Agnostic Pre-training and Task-Guided Fine-tuning for Versatile Diffusion Plannercited by 1
  38. 2024MF-LAL: Drug Compound Generation Using Multi-Fidelity Latent Space Active Learningcited by 1

50 most cited of 87 All 87 (JSON)

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  1. 2025Diffusion Models at the Drug Discovery Frontier: A Review on Generating Small Molecules versus Therapeutic Peptides
  2. 2023Navigating the Design Space of Equivariant Diffusion-Based Generative Models for De Novo 3D Molecule Generation
  3. 2025Pharmacophore-Conditioned Diffusion Model for Ligand-Based De Novo Drug Design
  4. 2024ShEPhERD: Diffusing shape, electrostatics, and pharmacophores for bioisosteric drug design
  5. 2022DiffDock: Diffusion Steps, Twists, and Turns for Molecular Docking
  6. 2026SynLaD: Latent Diffusion for Generating Synthesizable Molecules Conditioned on 3D Pharmacophore Profiles
  7. 2024Manifold-Constrained Nucleus-Level Denoising Diffusion Model for Structure-Based Drug Design
  8. 2022DiffMD: A Geometric Diffusion Model for Molecular Dynamics Simulations