用自回归扩散模型生成3D分子,支持任意长度和片段条件生成。
Autoregressive latent diffusion for 3D molecule generation

- 在预训练编码器的隐空间中联合建模分子拓扑与几何结构。
- 在QM9和GEOM-Drugs上达到自回归方法领先性能,接近扩散模型水平。
- 单模型实现无条件与片段条件生成,适合药物分子设计场景。
三维分子生成长期由扩散模型主导,虽生成质量高,但需预先指定分子大小。近期自回归方法显著缩小了性能差距,天然支持可变长度生成并能基于部分分子上下文进行条件生成,但如何平衡无条件与条件生成仍具挑战。我们提出KRONOS,一种基于预训练自编码器隐空间的自回归扩散框架,联合建模分子图拓扑与几何结构,同时保持自回归生成的灵活性。我们进一步引入受填中间(FIM)范式启发的混合训练策略,使单一从左到右的自回归模型可同时实现无条件与片段条件分子生成。在QM9和GEOM-Drugs数据集上的实验表明,KRONOS在自回归方法中达到领先的无条件生成性能,且与扩散模型相当;同时,片段条件生成对无条件性能影响微乎其微,证明两种生成范式可在同一架构中有效共存。
原文摘要 · Abstract (English)
Three-dimensional (3D) molecule generation has been dominated by diffusion models, which achieve strong generation quality but typically require the molecular size to be specified a priori. Recent autoregressive approaches have substantially narrowed the performance gap while naturally supporting variable-length generation and conditioning on partial molecular context. However, balancing unconditional and context-conditioned generation remains challenging. We introduce KRONOS, a latent autoregressive diffusion framework that generates molecules in the latent space of a pre-trained autoencoder, jointly modeling molecular graph topology and geometry, while retaining the flexibility of autoregressive generation. We further introduce a mixed training strategy inspired by Fill-in-the Middle (FIM) paradigm, enabling both unconditional and fragment-conditioned molecular generation within a single left-to-right autoregressive model. Experiments on QM9 and GEOM-Drugs demonstrate that KRONOS achieves leading unconditional generation performance among autoregressive methods, while remaining competitive with diffusion models. Moreover, fragment-conditioned generation is achieved with negligible impact on unconditional generation performance, demonstrating that both generation paradigms can be supported within a single architecture.
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