arXiv:2509.15242cs.CV2025-09

用合成原子力显微镜图像训练模型,实现蛋白质复合物高精度3D重建。

ProFusion: 3D Reconstruction of Protein Complex Structures from Multi-view AFM Images

  • 结合虚拟AFM模拟与扩散模型生成多视角图像
  • 重建结构的平均切比雪夫距离达到AFM分辨率水平
  • 适合需要快速低成本验证蛋白复合物结构的研究者

基于AI的计算方法在蛋白结构预测中表现优异,但在涉及多个相互作用蛋白的大规模蛋白质复合物(PCs)上因缺乏三维空间信息而受限。实验技术如冷冻电镜虽准确但成本高、耗时长。本文提出ProFusion,一种融合深度学习与原子力显微镜(AFM)的混合框架。AFM可从随机取向获取高分辨率高度图,天然提供多视角数据用于3D重建。然而,构建大规模真实AFM数据集以训练深度学习模型不现实。为此,我们开发了虚拟AFM框架,模拟成像过程,生成约54.2万条含多视角合成AFM图像的蛋白数据。训练条件扩散模型以从无姿态输入合成新视角,并采用实例特定的神经辐射场(NeRF)模型进行3D结构重建。重建结果在平均切比雪夫距离上达到AFM成像分辨率,体现高结构保真度。方法在多种蛋白质复合物的实验AFM图像上广泛验证,展现出高精度、低成本的蛋白质复合物结构预测潜力,支持利用AFM实验进行快速迭代验证。

原文摘要 · Abstract (English)

AI-based in silico methods have improved protein structure prediction but often struggle with large protein complexes (PCs) involving multiple interacting proteins due to missing 3D spatial cues. Experimental techniques like Cryo-EM are accurate but costly and time-consuming. We present ProFusion, a hybrid framework that integrates a deep learning model with Atomic Force Microscopy (AFM), which provides high-resolution height maps from random orientations, naturally yielding multi-view data for 3D reconstruction. However, generating a large-scale AFM imaging data set sufficient to train deep learning models is impractical. Therefore, we developed a virtual AFM framework that simulates the imaging process and generated a dataset of ~542,000 proteins with multi-view synthetic AFM images. We train a conditional diffusion model to synthesize novel views from unposed inputs and an instance-specific Neural Radiance Field (NeRF) model to reconstruct 3D structures. Our reconstructed 3D protein structures achieve an average Chamfer Distance within the AFM imaging resolution, reflecting high structural fidelity. Our method is extensively validated on experimental AFM images of various PCs, demonstrating strong potential for accurate, cost-effective protein complex structure prediction and rapid iterative validation using AFM experiments.

3D重建蛋白质结构原子力显微镜扩散模型

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