# Autoregressive latent diffusion for 3D molecule generation

arXiv: https://arxiv.org/abs/2607.09277 · HTML: https://mlsanity.com/paper/2607.09277/

## Key facts

- Cited by 1 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 33 of its 43 references that are in the map.
- First posted on arXiv 10 Jul 2026.

## 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 33)

- [Attention Is All You Need](https://mlsanity.com/paper/1706.03762/) (2017)
- [BERT: Pre-training of Deep Bidirectional Transformers for Language Understanding](https://mlsanity.com/paper/1810.04805/) (2018)
- [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)
- [Elucidating the Design Space of Diffusion-Based Generative Models](https://mlsanity.com/paper/2206.00364/) (2022)
- [XLNet: Generalized Autoregressive Pretraining for Language Understanding](https://mlsanity.com/paper/1906.08237/) (2019)
- [MaskGIT: Masked Generative Image Transformer](https://mlsanity.com/paper/2202.04200/) (2022)
- [Equivariant Diffusion for Molecule Generation in 3D](https://mlsanity.com/paper/2203.17003/) (2022)
- [Autoregressive Image Generation without Vector Quantization](https://mlsanity.com/paper/2406.11838/) (2024)
- [The Impact of Positional Encoding on Length Generalization in Transformers](https://mlsanity.com/paper/2305.19466/) (2023)
- [Efficient Training of Language Models to Fill in the Middle](https://mlsanity.com/paper/2207.14255/) (2022)
- [GEOM: Energy-annotated molecular conformations for property prediction and molecular generation](https://mlsanity.com/paper/2006.05531/) (2020)
- [Autoregressive Diffusion Models](https://mlsanity.com/paper/2110.02037/) (2021)
- [Geometric Latent Diffusion Models for 3D Molecule Generation](https://mlsanity.com/paper/2305.01140/) (2023)
- [Symmetry-adapted generation of 3d point sets for the targeted discovery of molecules](https://mlsanity.com/paper/1906.00957/) (2019)
- [Motif-based Graph Self-Supervised Learning for Molecular Property Prediction](https://mlsanity.com/paper/2110.00987/) (2021)
- [Transformer Language Models without Positional Encodings Still Learn Positional Information](https://mlsanity.com/paper/2203.16634/) (2022)
- [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)
- [Neural Autoregressive Distribution Estimation](https://mlsanity.com/paper/1605.02226/) (2016)
- [All-atom Diffusion Transformers: Unified generative modelling of molecules and materials](https://mlsanity.com/paper/2503.03965/) (2025)
- [Relational Attention: Generalizing Transformers for Graph-Structured Tasks](https://mlsanity.com/paper/2210.05062/) (2022)
- [Improving Molecular Contrastive Learning via Faulty Negative Mitigation and Decomposed Fragment Contrast](https://mlsanity.com/paper/2202.09346/) (2022)
- [Guiding Generative Models to Uncover Diverse and Novel Crystals via Reinforcement Learning](https://mlsanity.com/paper/2511.07158/) (2025)
- [Symphony: Symmetry-Equivariant Point-Centered Spherical Harmonics for 3D Molecule Generation](https://mlsanity.com/paper/2311.16199/) (2023)
- [Towards Unified and Lossless Latent Space for 3D Molecular Latent Diffusion Modeling](https://mlsanity.com/paper/2503.15567/) (2025)
- [Scalable Autoregressive 3D Molecule Generation](https://mlsanity.com/paper/2505.13791/) (2025)
- [FragFM: Hierarchical Framework for Efficient Molecule Generation via Fragment-Level Discrete Flow Matching](https://mlsanity.com/paper/2502.15805/) (2025)
- [Graph Diffusion Transformers are In-Context Molecular Designers](https://mlsanity.com/paper/2510.08744/) (2025)

## Built on by (most cited first, 1 of 1)

- [Fixed-Dimensional Latent Flow for Generating Variable-Size 3D Molecules](https://mlsanity.com/paper/2609.08333/) (2026)

## Abstract (arXiv)

Three-dimensional (3D) molecule generation has been dominated by diffusion models, which achieve strong generation quality but typically require molecular size to be specified (or predicted) separately before generation. This can be limiting for fragment-based molecule generation, central to drug discovery, where the size of the generated structure is itself part of the design problem. Autoregressive models determine size during generation and naturally support partial-structure conditioning, but balancing unconditional and fragment-conditioned generation remains challenging. We introduce KRONOS, a latent autoregressive diffusion framework that generates molecules in the latent space of a Unified AutoEncoder (UAE), jointly modeling molecular graph topology and geometry, while retaining the flexibility of autoregressive generation. We further introduce a mixed training strategy inspired by the Fill-in-the-Middle (FIM) paradigm, enabling a single left-to-right autoregressive model to support both unconditional and fragment-conditioned generation. Experiments on QM9 and GEOM-Drugs demonstrate strong unconditional generation performance and competitive fragment-conditioned generation.