用扩散模型联合设计蛋白结构与表面，实现精准匹配目标受体。
Joint Design of Protein Surface and Structure Using a Diffusion Bridge Model
- 通过扩散桥模型将受体表面映射为配体表面，生成互补结构。
- 多模型扩散预测结构，几何与骨架对齐提升稳定性与可行性。
- 适用于药物设计等需要精确结合的蛋白改造任务。
蛋白质-蛋白质相互作用（PPIs）由界面处的表面互补性和疏水作用调控。然而，在计算蛋白质设计中，同时生成多样且物理上合理的蛋白结构与表面以精确匹配目标受体仍具挑战。本文提出PepBridge框架，实现蛋白表面与结构的联合设计，无缝整合受体表面几何形状与生化特性。以3D点云形式表示受体表面，PepBridge通过多步流程生成完整蛋白结构：首先使用去噪扩散桥模型（DDBMs）将受体表面映射至配体表面；随后，多模型扩散模型预测对应结构，而形状-框架匹配网络确保表面几何与骨架架构的一致性。该集成方法促进表面互补性、构象稳定性和化学可行性。在多种蛋白设计场景中的广泛验证表明，PepBridge能有效生成结构可行的蛋白，显著推进了自上而下的蛋白结构联合设计。
原文摘要 · Abstract (English)
Protein-protein interactions (PPIs) are governed by surface complementarity and hydrophobic interactions at protein interfaces. However, designing diverse and physically realistic protein structure and surfaces that precisely complement target receptors remains a significant challenge in computational protein design. In this work, we introduce PepBridge, a novel framework for the joint design of protein surface and structure that seamlessly integrates receptor surface geometry and biochemical properties. Starting with a receptor surface represented as a 3D point cloud, PepBridge generates complete protein structures through a multi-step process. First, it employs denoising diffusion bridge models (DDBMs) to map receptor surfaces to ligand surfaces. Next, a multi-model diffusion model predicts the corresponding structure, while Shape-Frame Matching Networks ensure alignment between surface geometry and backbone architecture. This integrated approach facilitates surface complementarity, conformational stability, and chemical feasibility. Extensive validation across diverse protein design scenarios demonstrates PepBridge's efficacy in generating structurally viable proteins, representing a significant advancement in the joint design of top-down protein structure.
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