# ControlMol: Adding Substructure Control To Molecule Diffusion Models

arXiv: https://arxiv.org/abs/2405.06659 · HTML: https://mlsanity.com/paper/2405.06659/

## Key facts

- Cited by 2 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 28 of its 34 references that are in the map.
- First posted on arXiv 22 Apr 2024.

## 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, 28 of 28)

- [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)
- [High-Resolution Image Synthesis with Latent Diffusion Models](https://mlsanity.com/paper/2112.10752/) (2021)
- [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)
- [Adding Conditional Control to Text-to-Image Diffusion Models](https://mlsanity.com/paper/2302.05543/) (2023)
- [RePaint: Inpainting using Denoising Diffusion Probabilistic Models](https://mlsanity.com/paper/2201.09865/) (2022)
- [T2I-Adapter: Learning Adapters to Dig out More Controllable Ability for Text-to-Image Diffusion Models](https://mlsanity.com/paper/2302.08453/) (2023)
- [E(n) Equivariant Graph Neural Networks](https://mlsanity.com/paper/2102.09844/) (2021)
- [GLIGEN: Open-Set Grounded Text-to-Image Generation](https://mlsanity.com/paper/2301.07093/) (2023)
- [Equivariant Diffusion for Molecule Generation in 3D](https://mlsanity.com/paper/2203.17003/) (2022)
- [A Generalization of Transformer Networks to Graphs](https://mlsanity.com/paper/2012.09699/) (2020)
- [Argmax Flows and Multinomial Diffusion: Learning Categorical Distributions](https://mlsanity.com/paper/2102.05379/) (2021)
- [SchNet: A continuous-filter convolutional neural network for modeling quantum interactions](https://mlsanity.com/paper/1706.08566/) (2017)
- [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)
- [Emu Edit: Precise Image Editing via Recognition and Generation Tasks](https://mlsanity.com/paper/2311.10089/) (2023)
- [Molecular Sets (MOSES): A Benchmarking Platform for Molecular Generation Models](https://mlsanity.com/paper/1811.12823/) (2018)
- [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)
- [Symmetry-adapted generation of 3d point sets for the targeted discovery of molecules](https://mlsanity.com/paper/1906.00957/) (2019)
- [E(n) Equivariant Normalizing Flows](https://mlsanity.com/paper/2105.09016/) (2021)
- [Equivariant 3D-Conditional Diffusion Models for Molecular Linker Design](https://mlsanity.com/paper/2210.05274/) (2022)
- [MiDi: Mixed Graph and 3D Denoising Diffusion for Molecule Generation](https://mlsanity.com/paper/2302.09048/) (2023)
- [MDM: Molecular Diffusion Model for 3D Molecule Generation](https://mlsanity.com/paper/2209.05710/) (2022)
- [Conditional molecular design with deep generative models](https://mlsanity.com/paper/1805.00108/) (2018)

## Built on by (most cited first, 2 of 2)

- [SubGDiff: A Subgraph Diffusion Model to Improve Molecular Representation Learning](https://mlsanity.com/paper/2405.05665/) (2024)
- [Efficient Antibody Structure Refinement Using Energy-Guided SE(3) Flow Matching](https://mlsanity.com/paper/2410.16673/) (2024)

## Abstract (arXiv)

Due to the vast design space of molecules, generating molecules conditioned on a specific sub-structure relevant to a particular function or therapeutic target is a crucial task in computer-aided drug design. Existing works mainly focus on specific tasks, such as linker design or scaffold hopping, each task requires training a model from scratch, and many well-pretrained De Novo molecule generation model parameters are not effectively utilized. To this end, we propose a two-stage training approach, consisting of condition learning and condition optimization. In the condition learning stage, we adopt the idea of ControlNet and design some meaningful adjustments to make the unconditional generative model learn sub-structure conditioned generation. In the condition optimization stage, by using human preference learning, we further enhance the stability and robustness of sub-structure control. In our experiments, only trained on randomly partitioned sub-structure data, the proposed method outperforms previous techniques by generating more valid and diverse molecules. Our method is easy to implement and can be quickly applied to various pre-trained molecule generation models.