# Diffusion-based Molecule Generation with Informative Prior Bridges

arXiv: https://arxiv.org/abs/2209.00865 · HTML: https://mlsanity.com/paper/2209.00865/

## Key facts

- Cited by 106 papers in the map (data through 14 Oct 2026).
- Builds on 32 of its 55 references that are in the map.
- First posted on arXiv 2 Sep 2022.

## Builds on (most cited first, 30 of 32)

- [Denoising Diffusion Probabilistic Models](https://mlsanity.com/paper/2006.11239/) (2020)
- [Denoising Diffusion Implicit Models](https://mlsanity.com/paper/2010.02502/) (2020)
- [Score-Based Generative Modeling through Stochastic Differential Equations](https://mlsanity.com/paper/2011.13456/) (2020)
- [Deep Unsupervised Learning using Nonequilibrium Thermodynamics](https://mlsanity.com/paper/1503.03585/) (2015)
- [ShapeNet: An Information-Rich 3D Model Repository](https://mlsanity.com/paper/1512.03012/) (2015)
- [Diffusion Probabilistic Models for 3D Point Cloud Generation](https://mlsanity.com/paper/2103.01458/) (2021)
- [Equivariant Diffusion for Molecule Generation in 3D](https://mlsanity.com/paper/2203.17003/) (2022)
- [Maximum Likelihood Training of Score-Based Diffusion Models](https://mlsanity.com/paper/2101.09258/) (2021)
- [Diffusion Schr"odinger Bridge with Applications to Score-Based Generative Modeling](https://mlsanity.com/paper/2106.01357/) (2021)
- [3D Shape Generation and Completion through Point-Voxel Diffusion](https://mlsanity.com/paper/2104.03670/) (2021)
- [GeoDiff: a Geometric Diffusion Model for Molecular Conformation Generation](https://mlsanity.com/paper/2203.02923/) (2022)
- [PointFlow: 3D Point Cloud Generation with Continuous Normalizing Flows](https://mlsanity.com/paper/1906.12320/) (2019)
- [Torsional Diffusion for Molecular Conformer Generation](https://mlsanity.com/paper/2206.01729/) (2022)
- [Pre-training Molecular Graph Representation with 3D Geometry](https://mlsanity.com/paper/2110.07728/) (2021)
- [Learning Gradient Fields for Shape Generation](https://mlsanity.com/paper/2008.06520/) (2020)
- [GEOM: Energy-annotated molecular conformations for property prediction and molecular generation](https://mlsanity.com/paper/2006.05531/) (2020)
- [Likelihood Training of Schr"odinger Bridge using Forward-Backward SDEs Theory](https://mlsanity.com/paper/2110.11291/) (2021)
- [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)
- [Learning Gradient Fields for Molecular Conformation Generation](https://mlsanity.com/paper/2105.03902/) (2021)
- [Solving Schr"odinger Bridges via Maximum Likelihood](https://mlsanity.com/paper/2106.02081/) (2021)
- [Deep Generative Learning via Schr"odinger Bridge](https://mlsanity.com/paper/2106.10410/) (2021)
- [Let us Build Bridges: Understanding and Extending Diffusion Generative Models](https://mlsanity.com/paper/2208.14699/) (2022)
- [Molecular geometry prediction using a deep generative graph neural network](https://mlsanity.com/paper/1904.00314/) (2019)
- [Learning Neural Generative Dynamics for Molecular Conformation Generation](https://mlsanity.com/paper/2102.10240/) (2021)
- [A Generative Model for Molecular Distance Geometry](https://mlsanity.com/paper/1909.11459/) (2019)
- [MolGenSurvey: A Systematic Survey in Machine Learning Models for Molecule Design](https://mlsanity.com/paper/2203.14500/) (2022)
- [An End-to-End Framework for Molecular Conformation Generation via Bilevel Programming](https://mlsanity.com/paper/2105.07246/) (2021)
- [Equivariant Point Cloud Analysis via Learning Orientations for Message Passing](https://mlsanity.com/paper/2203.14486/) (2022)
- [Accurate De Novo Prediction of Protein Contact Map by Ultra-Deep Learning Model](https://mlsanity.com/paper/1609.00680/) (2016)

## Built on by (most cited first, 30 of 106)

- [Flow Straight and Fast: Learning to Generate and Transfer Data with Rectified Flow](https://mlsanity.com/paper/2209.03003/) (2022)
- [DPM-Solver++: Fast Solver for Guided Sampling of Diffusion Probabilistic Models](https://mlsanity.com/paper/2211.01095/) (2022)
- [InstaFlow: One Step is Enough for High-Quality Diffusion-Based Text-to-Image Generation](https://mlsanity.com/paper/2309.06380/) (2023)
- [DiffusionDet: Diffusion Model for Object Detection](https://mlsanity.com/paper/2211.09788/) (2022)
- [DIFUSCO: Graph-based Diffusion Solvers for Combinatorial Optimization](https://mlsanity.com/paper/2302.08224/) (2023)
- [Geometric Latent Diffusion Models for 3D Molecule Generation](https://mlsanity.com/paper/2305.01140/) (2023)
- [Contrastive Energy Prediction for Exact Energy-Guided Diffusion Sampling in Offline Reinforcement Learning](https://mlsanity.com/paper/2304.12824/) (2023)
- [Fine-Tuning of Continuous-Time Diffusion Models as Entropy-Regularized Control](https://mlsanity.com/paper/2402.15194/) (2024)
- [Generative Diffusion Models on Graphs: Methods and Applications](https://mlsanity.com/paper/2302.02591/) (2023)
- [Diffusion Bridge Mixture Transports, Schr"odinger Bridge Problems and Generative Modeling](https://mlsanity.com/paper/2304.00917/) (2023)
- [An Overview of Diffusion Models: Applications, Guided Generation, Statistical Rates and Optimization](https://mlsanity.com/paper/2404.07771/) (2024)
- [MolDiff: Addressing the Atom-Bond Inconsistency Problem in 3D Molecule Diffusion Generation](https://mlsanity.com/paper/2305.07508/) (2023)
- [Equivariant Flow Matching with Hybrid Probability Transport](https://mlsanity.com/paper/2312.07168/) (2023)
- [Fast Point Cloud Generation with Straight Flows](https://mlsanity.com/paper/2212.01747/) (2022)
- [Graph Generation with Diffusion Mixture](https://mlsanity.com/paper/2302.03596/) (2023)
- [Navigating the Design Space of Equivariant Diffusion-Based Generative Models for De Novo 3D Molecule Generation](https://mlsanity.com/paper/2309.17296/) (2023)
- [AdaFlow: Imitation Learning with Variance-Adaptive Flow-Based Policies](https://mlsanity.com/paper/2402.04292/) (2024)
- [3D molecule generation by denoising voxel grids](https://mlsanity.com/paper/2306.07473/) (2023)
- [Geometry-Complete Diffusion for 3D Molecule Generation and Optimization](https://mlsanity.com/paper/2302.04313/) (2023)
- [A Survey on Graph Diffusion Models: Generative AI in Science for Molecule, Protein and Material](https://mlsanity.com/paper/2304.01565/) (2023)
- [SlimFlow: Training Smaller One-Step Diffusion Models with Rectified Flow](https://mlsanity.com/paper/2407.12718/) (2024)
- [Learning Joint 2D & 3D Diffusion Models for Complete Molecule Generation](https://mlsanity.com/paper/2305.12347/) (2023)
- [Doob's Lagrangian: A Sample-Efficient Variational Approach to Transition Path Sampling](https://mlsanity.com/paper/2410.07974/) (2024)
- [Energy Matching: Unifying Flow Matching and Energy-Based Models for Generative Modeling](https://mlsanity.com/paper/2504.10612/) (2025)
- [Towards Symmetry-Aware Generation of Periodic Materials](https://mlsanity.com/paper/2307.02707/) (2023)
- [Diffusion Models in textitDe Novo Drug Design](https://mlsanity.com/paper/2406.08511/) (2024)
- [DiffPack: A Torsional Diffusion Model for Autoregressive Protein Side-Chain Packing](https://mlsanity.com/paper/2306.01794/) (2023)
- [OFTSR: One-Step Flow for Image Super-Resolution with Tunable Fidelity-Realism Trade-offs](https://mlsanity.com/paper/2412.09465/) (2024)
- [Generative Modeling on Manifolds Through Mixture of Riemannian Diffusion Processes](https://mlsanity.com/paper/2310.07216/) (2023)
- [UniGEM: A Unified Approach to Generation and Property Prediction for Molecules](https://mlsanity.com/paper/2410.10516/) (2024)

## Abstract (arXiv)

AI-based molecule generation provides a promising approach to a large area of biomedical sciences and engineering, such as antibody design, hydrolase engineering, or vaccine development. Because the molecules are governed by physical laws, a key challenge is to incorporate prior information into the training procedure to generate high-quality and realistic molecules. We propose a simple and novel approach to steer the training of diffusion-based generative models with physical and statistics prior information. This is achieved by constructing physically informed diffusion bridges, stochastic processes that guarantee to yield a given observation at the fixed terminal time. We develop a Lyapunov function based method to construct and determine bridges, and propose a number of proposals of informative prior bridges for both high-quality molecule generation and uniformity-promoted 3D point cloud generation. With comprehensive experiments, we show that our method provides a powerful approach to the 3D generation task, yielding molecule structures with better quality and stability scores and more uniformly distributed point clouds of high qualities.