# Lift Your Molecules: Molecular Graph Generation in Latent Euclidean Space

arXiv: https://arxiv.org/abs/2406.10513 · HTML: https://mlsanity.com/paper/2406.10513/

## Key facts

- Cited by 8 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 44 of its 62 references that are in the map.
- First posted on arXiv 15 Jun 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, 30 of 44)

- [Denoising Diffusion Probabilistic Models](https://mlsanity.com/paper/2006.11239/) (2020)
- [PyTorch: An Imperative Style, High-Performance Deep Learning Library](https://mlsanity.com/paper/1912.01703/) (2019)
- [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)
- [Deep Unsupervised Learning using Nonequilibrium Thermodynamics](https://mlsanity.com/paper/1503.03585/) (2015)
- [Classifier-Free Diffusion Guidance](https://mlsanity.com/paper/2207.12598/) (2022)
- [Generative Modeling by Estimating Gradients of the Data Distribution](https://mlsanity.com/paper/1907.05600/) (2019)
- [Improved Denoising Diffusion Probabilistic Models](https://mlsanity.com/paper/2102.09672/) (2021)
- [Elucidating the Design Space of Diffusion-Based Generative Models](https://mlsanity.com/paper/2206.00364/) (2022)
- [Structured Denoising Diffusion Models in Discrete State-Spaces](https://mlsanity.com/paper/2107.03006/) (2021)
- [E(n) Equivariant Graph Neural Networks](https://mlsanity.com/paper/2102.09844/) (2021)
- [Automatic chemical design using a data-driven continuous representation of molecules](https://mlsanity.com/paper/1610.02415/) (2016)
- [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)
- [Score-based Generative Modeling in Latent Space](https://mlsanity.com/paper/2106.05931/) (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)
- [Analyzing and Improving the Training Dynamics of Diffusion Models](https://mlsanity.com/paper/2312.02696/) (2023)
- [GraphAF: a Flow-based Autoregressive Model for Molecular Graph Generation](https://mlsanity.com/paper/2001.09382/) (2020)
- [GuacaMol: Benchmarking Models for De Novo Molecular Design](https://mlsanity.com/paper/1811.09621/) (2018)
- [Score-based Generative Modeling of Graphs via the System of Stochastic Differential Equations](https://mlsanity.com/paper/2202.02514/) (2022)
- [Molecular Sets (MOSES): A Benchmarking Platform for Molecular Generation Models](https://mlsanity.com/paper/1811.12823/) (2018)
- [Permutation Invariant Graph Generation via Score-Based Generative Modeling](https://mlsanity.com/paper/2003.00638/) (2020)
- [Learning Deep Generative Models of Graphs](https://mlsanity.com/paper/1803.03324/) (2018)
- [Structure-based Drug Design with Equivariant Diffusion Models](https://mlsanity.com/paper/2210.13695/) (2022)
- [Hierarchical Generation of Molecular Graphs using Structural Motifs](https://mlsanity.com/paper/2002.03230/) (2020)
- [Fr'echet ChemNet Distance: A metric for generative models for molecules in drug discovery](https://mlsanity.com/paper/1803.09518/) (2018)
- [Diagnosing and Enhancing VAE Models](https://mlsanity.com/paper/1903.05789/) (2019)

## Built on by (most cited first, 8 of 8)

- [Unified Guidance for Geometry-Conditioned Molecular Generation](https://mlsanity.com/paper/2501.02526/) (2025)
- [Graph Diffusion that can Insert and Delete](https://mlsanity.com/paper/2506.15725/) (2025)
- [Principled Latent Diffusion for Graphs via Laplacian Autoencoders](https://mlsanity.com/paper/2601.13780/) (2026)
- [Predictive Feature Caching for Training-free Acceleration of Molecular Geometry Generation](https://mlsanity.com/paper/2510.04646/) (2025)
- [GraViti: Graph-Level Variational Autoencoders with Relaxed Permutation Invariance](https://mlsanity.com/paper/2605.16668/) (2026)
- [Breaking the Bottlenecks: Scalable Diffusion Models for 3D Molecular Generation](https://mlsanity.com/paper/2601.08963/) (2026)
- [GeoGAE: Scalable Graph-Level Autoencoding via Hyperball Cloud Representations](https://mlsanity.com/paper/2609.35527/) (2026)
- [MIRRA: Fast, High-Fidelity Molecular Generation with Chemistry-Informed Discrete Flow Matching](https://mlsanity.com/paper/2610.17244/) (2026)

## Abstract (arXiv)

We introduce a new framework for molecular graph generation with 3D molecular generative models. Our Synthetic Coordinate Embedding (SyCo) framework maps molecular graphs to Euclidean point clouds via synthetic conformer coordinates and learns the inverse map using an E(n)-Equivariant Graph Neural Network (EGNN). The induced point cloud-structured latent space is well-suited to apply existing 3D molecular generative models. This approach simplifies the graph generation problem - without relying on molecular fragments nor autoregressive decoding - into a point cloud generation problem followed by node and edge classification tasks. Further, we propose a novel similarity-constrained optimization scheme for 3D diffusion models based on inpainting and guidance. As a concrete implementation of our framework, we develop EDM-SyCo based on the E(3) Equivariant Diffusion Model (EDM). EDM-SyCo achieves state-of-the-art performance in distribution learning of molecular graphs, outperforming the best non-autoregressive methods by more than 30% on ZINC250K and 16% on the large-scale GuacaMol dataset while improving conditional generation by up to 3.9 times.