通过跨盒交互建模,提升冷冻电镜蛋白结构图的表示能力。
CryoProt: A Protein Pretraining Framework with Cross-Box Interactions on Cryo-EM Density Maps

- 引入共享潜空间的多头隐式注意力,显式建模密度图中盒子间的跨域依赖。
- 在多个下游任务中表现优于现有方法,最高提升达12%。
- 适用于蛋白柔韧性等预测任务,无需额外标注数据即可迁移使用。
尽管冷冻电镜(cryo-EM)密度图数据日益丰富,但有效利用其进行蛋白质表征仍具挑战。首先,当前方法缺乏专为cryo-EM密度图设计的通用蛋白质预训练框架,用于蛋白相关属性预测。其次,现有方法通常将密度图划分为局部盒子并独立建模,忽略了跨盒子的相互作用,而这些交互对捕捉冷冻电镜密度图中的全局结构上下文至关重要。为此,我们提出CryoProt,一种专为冷冻电镜密度图设计的蛋白质预训练框架。CryoProt采用基于多头隐式注意力(MLA)的图编码器,使盒子级表征通过共享潜空间交互,从而显式建模密度图内的跨盒依赖关系。此外,我们采用多任务预训练策略,学习可泛化到多种下游任务的表示,如蛋白柔韧性预测——该任务无需直接使用冷冻电镜密度图,模型可通过预训练隐式推断。实验表明,CryoProt在多个基准测试中持续优于现有最先进方法,性能最高提升达12%,凸显了在冷冻电镜数据中建模跨盒交互的重要性。源代码已公开于https://anonymous.4open.science/r/CryoProt。
原文摘要 · Abstract (English)
Despite the growing availability of cryo-electron microscopy (cryo-EM) density maps, effectively leveraging them for protein representation remains challenging. First, current methods lack a general-purpose protein pretraining framework tailored for cryo-EM density maps, designed for protein-related property prediction. Second, existing approaches typically partition density maps into local box regions and model them independently, overlooking interactions across boxes which are essential for capturing global structural context in cryo-EM density map. To address these challenges, we propose CryoProt, a protein pretraining framework designed for cryo-EM density maps. CryoProt introduces a Map Encoder based on multi-head latent attention (MLA), where box-level representations interact through a shared latent space, enabling explicit modeling of cross-box dependencies within the density map. Furthermore, we adopt a multi-task pretraining strategy to learn generalizable representations that can be effectively transferred to diverse downstream tasks, such as protein flexibility prediction, where cryo-EM density maps are not required and can be inferred implicitly by the pretrained model. Experimental results demonstrate that CryoProt consistently outperforms existing state-of-the-art methods across multiple benchmarks, achieving up to 12% improvement over the best-performing baselines, highlighting the importance of modeling cross-box interactions in cryo-EM data. The source code is publicly available at https://anonymous.4open.science/r/CryoProt.
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