# Unraveling the Potential of Diffusion Models in Small Molecule Generation

arXiv: https://arxiv.org/abs/2507.08005 · HTML: https://mlsanity.com/paper/2507.08005/

## Key facts

- Cited by 3 papers 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 52 of its 85 references that are in the map.
- First posted on arXiv 25 Jun 2025.

## Placed in

- Diffusion models / [Flow matching, time series and science](https://mlsanity.com/diffusion/flow-matching-time-series-and-science/)

## Builds on (most cited first, 30 of 52)

- [Denoising Diffusion Probabilistic Models](https://mlsanity.com/paper/2006.11239/) (2020)
- [U-Net: Convolutional Networks for Biomedical Image Segmentation](https://mlsanity.com/paper/1505.04597/) (2015)
- [Training language models to follow instructions with human feedback](https://mlsanity.com/paper/2203.02155/) (2022)
- [Score-Based Generative Modeling through Stochastic Differential Equations](https://mlsanity.com/paper/2011.13456/) (2020)
- [Diffusion Models Beat GANs on Image Synthesis](https://mlsanity.com/paper/2105.05233/) (2021)
- [Classifier-Free Diffusion Guidance](https://mlsanity.com/paper/2207.12598/) (2022)
- [Flow Matching for Generative Modeling](https://mlsanity.com/paper/2210.02747/) (2022)
- [Generative Modeling by Estimating Gradients of the Data Distribution](https://mlsanity.com/paper/1907.05600/) (2019)
- [Graph Neural Networks: A Review of Methods and Applications](https://mlsanity.com/paper/1812.08434/) (2018)
- [RePaint: Inpainting using Denoising Diffusion Probabilistic Models](https://mlsanity.com/paper/2201.09865/) (2022)
- [Diffusion-LM Improves Controllable Text Generation](https://mlsanity.com/paper/2205.14217/) (2022)
- [E(n) Equivariant Graph Neural Networks](https://mlsanity.com/paper/2102.09844/) (2021)
- [Equivariant Diffusion for Molecule Generation in 3D](https://mlsanity.com/paper/2203.17003/) (2022)
- [Junction Tree Variational Autoencoder for Molecular Graph Generation](https://mlsanity.com/paper/1802.04364/) (2018)
- [ILVR: Conditioning Method for Denoising Diffusion Probabilistic Models](https://mlsanity.com/paper/2108.02938/) (2021)
- [SE(3)-Transformers: 3D Roto-Translation Equivariant Attention Networks](https://mlsanity.com/paper/2006.10503/) (2020)
- [DiGress: Discrete Denoising diffusion for graph generation](https://mlsanity.com/paper/2209.14734/) (2022)
- [GeoDiff: a Geometric Diffusion Model for Molecular Conformation Generation](https://mlsanity.com/paper/2203.02923/) (2022)
- [MolGAN: An implicit generative model for small molecular graphs](https://mlsanity.com/paper/1805.11973/) (2018)
- [GraphVAE: Towards Generation of Small Graphs Using Variational Autoencoders](https://mlsanity.com/paper/1802.03480/) (2018)
- [Analog Bits: Generating Discrete Data using Diffusion Models with Self-Conditioning](https://mlsanity.com/paper/2208.04202/) (2022)
- [DiffDock: Diffusion Steps, Twists, and Turns for Molecular Docking](https://mlsanity.com/paper/2210.01776/) (2022)
- [GuacaMol: Benchmarking Models for De Novo Molecular Design](https://mlsanity.com/paper/1811.09621/) (2018)
- [Fast High-Resolution Image Synthesis with Latent Adversarial Diffusion Distillation](https://mlsanity.com/paper/2403.12015/) (2024)
- [Torsional Diffusion for Molecular Conformer Generation](https://mlsanity.com/paper/2206.01729/) (2022)
- [GEOM: Energy-annotated molecular conformations for property prediction and molecular generation](https://mlsanity.com/paper/2006.05531/) (2020)
- [Structure-based Drug Design with Equivariant Diffusion Models](https://mlsanity.com/paper/2210.13695/) (2022)
- [Geometric Latent Diffusion Models for 3D Molecule Generation](https://mlsanity.com/paper/2305.01140/) (2023)
- [Translation between Molecules and Natural Language](https://mlsanity.com/paper/2204.11817/) (2022)
- [E(n) Equivariant Normalizing Flows](https://mlsanity.com/paper/2105.09016/) (2021)

## Built on by (most cited first, 3 of 3)

- [Diffusion Models at the Drug Discovery Frontier: A Review on Generating Small Molecules versus Therapeutic Peptides](https://mlsanity.com/paper/2511.00209/) (2025)
- [VEDA: 3D Molecular Generation via Variance-Exploding Diffusion with Annealing](https://mlsanity.com/paper/2511.09568/) (2025)
- [PocketVE: Stable and Property-Guided Structure-Based Drug Design with Variance-Exploding Diffusion](https://mlsanity.com/paper/2609.08101/) (2026)

## Abstract (arXiv)

Generative AI presents chemists with novel ideas for drug design and facilitates the exploration of vast chemical spaces. Diffusion models (DMs), an emerging tool, have recently attracted great attention in drug R&D. This paper comprehensively reviews the latest advancements and applications of DMs in molecular generation. It begins by introducing the theoretical principles of DMs. Subsequently, it categorizes various DM-based molecular generation methods according to their mathematical and chemical applications. The review further examines the performance of these models on benchmark datasets, with a particular focus on comparing the generation performance of existing 3D methods. Finally, it concludes by emphasizing current challenges and suggesting future research directions to fully exploit the potential of DMs in drug discovery.