mlsanityData to 14 Oct 2026

A 3D pocket-aware and evolutionary conserved interaction guided diffusion model for molecular optimization

arXiv 2505.05874 ↗First posted 9 May 2025cs.LG physics.chem-ph q-bio.BMcited by 1

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

Abstract (arXiv)

Generating molecules that bind to specific protein targets via diffusion models has shown good promise for structure-based drug design and molecule optimization. Especially, the diffusion models with binding interaction guidance enables molecule generation with high affinity through forming favorable interaction within protein pocket. However, the generated molecules may not form interactions with the highly conserved residues, which are important for protein functions and bioactivities of the ligands. Herein, we developed a new 3D target-aware diffusion model DiffDecip, which explicitly incorporates the protein-ligand binding interactions and evolutionary conservation information of protein residues into both diffusion and sampling process, for molecule optimization through scaffold decoration. The model performance revealed that DiffDecip outperforms baseline model DiffDec on molecule optimization towards higher affinity through forming more non-covalent interactions with highly conserved residues in the protein pocket.

Key facts. Cited by 1 paper in the map (data through 14 Oct 2026). Placed in Flow matching, time series and science, one of 14 directions in Diffusion models. Builds on 12 of its 37 references that are in the map. First posted on arXiv 9 May 2025.

Builds on

12 of 37 references.

Closest ancestors · 4

Same direction, newest first

  1. 2024DecompDiff: Diffusion Models with Decomposed Priors for Structure-Based Drug Design26 Feb
  2. 2022Structure-based Drug Design with Equivariant Diffusion Models24 Oct
  3. 2022Equivariant 3D-Conditional Diffusion Models for Molecular Linker Design11 Oct
  4. 2022Flow Matching for Generative Modeling6 Oct

Other references · 8

  1. 2020Denoising Diffusion Probabilistic Modelscited by 21,076
  2. 2020Score-Based Generative Modeling through Stochastic Differential Equationscited by 9,122
  3. 2015Deep Unsupervised Learning using Nonequilibrium Thermodynamicscited by 7,058
  4. 2021Improving language models by retrieving from trillions of tokenscited by 1,293
  5. 2021Variational Diffusion Modelscited by 1,153
  6. 20233D Equivariant Diffusion for Target-Aware Molecule Generation and Affinity Predictioncited by 177
  7. 2022A 3D Generative Model for Structure-Based Drug Designcited by 149
  8. 2022DiffBP: Generative Diffusion of 3D Molecules for Target Protein Bindingcited by 58

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Cited by year (2026 to 14 Oct)

Citing papers per year: 2026: 1.

1 paper.

  1. 2026FuseDiff: Symmetry-Preserving Joint Diffusion for Dual-Target Structure-Based Drug Designcited by 1

Similar, not cited

Close in wording, no citation either way

  1. 2025A 3D pocket-aware and affinity-guided diffusion model for lead optimization
  2. 2026Generating Developable 3D Molecules via Pocket-Conditioned Diffusion and Property-Aware Optimization
  3. 2024General Binding Affinity Guidance for Diffusion Models in Structure-Based Drug Design
  4. 2024Aligning Target-Aware Molecule Diffusion Models with Exact Energy Optimization
  5. 2026Fine-tuning Pocket-Aware Diffusion Models via Denoising Policy Optimization
  6. 2024BInD: Bond and Interaction-generating Diffusion Model for Multi-objective Structure-based Drug Design
  7. 2024Binding-Adaptive Diffusion Models for Structure-Based Drug Design
  8. 2026Do Language Models Dream of Binding Molecules? Benchmarking LLMs under Spatial Constraints