用离散结构令牌加速蛋白骨架生成,速度更快且结构更优。
SaDiT: Efficient Protein Backbone Design via Latent Structural Tokenization and Diffusion Transformers
- 将蛋白几何转为离散潜空间,降低生成复杂度。
- 采样速度比RFDiffusion快3.2倍,折叠成功率提升18%。
- 适合大规模蛋白设计与结构探索,尤其擅长复杂拓扑建模。
从头设计蛋白骨架的生成模型已取得显著进展,但基于扩散的方法仍计算密集,难以满足大规模结构探索需求。尽管近期如Proteina引入流匹配提升采样效率,但结构分词在蛋白领域的压缩与加速潜力尚未被充分挖掘。本文提出SaDiT框架,通过结合SaProt分词与扩散Transformer(DiT)架构,实现高效蛋白骨架生成。SaDiT利用离散潜空间表示蛋白几何,显著降低生成复杂度,同时保持SE(3)等价性。为进一步提升效率,引入IPA Token Cache机制,重用迭代采样中的计算状态以优化不变点注意力(IPA)层。实验表明,SaDiT在计算速度和结构可行性上均超越当前最优模型,包括RFDiffusion与Proteina。我们在无条件生成与折叠类别条件生成任务中评估,结果显示其在捕捉复杂拓扑特征方面具有更强的设计能力。
原文摘要 · Abstract (English)
Generative models for de novo protein backbone design have achieved remarkable success in creating novel protein structures. However, these diffusion-based approaches remain computationally intensive and slower than desired for large-scale structural exploration. While recent efforts like Proteina have introduced flow-matching to improve sampling efficiency, the potential of tokenization for structural compression and acceleration remains largely unexplored in the protein domain. In this work, we present SaDiT, a novel framework that accelerates protein backbone generation by integrating SaProt Tokenization with a Diffusion Transformer (DiT) architecture. SaDiT leverages a discrete latent space to represent protein geometry, significantly reducing the complexity of the generation process while maintaining theoretical SE(3) equivalence. To further enhance efficiency, we introduce an IPA Token Cache mechanism that optimizes the Invariant Point Attention (IPA) layers by reusing computed token states during iterative sampling. Experimental results demonstrate that SaDiT outperforms state-of-the-art models, including RFDiffusion and Proteina, in both computational speed and structural viability. We evaluate our model across unconditional backbone generation and fold-class conditional generation tasks, where SaDiT shows superior ability to capture complex topological features with high designability.
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