利用扩散桥模型联合设计蛋白质表面和结构
Joint Design of Protein Surface and Structure Using a Diffusion Bridge Model
AI总结：
PepBridge通过整合受体表面几何和生化性质，联合设计蛋白质表面和结构，提升蛋白质设计的物理合理性和结构可行性。
摘要：
蛋白质-蛋白质相互作用（PPIs）由蛋白质界面的表面互补性和疏水相互作用调控。然而，设计出多样且物理上合理的蛋白质结构和表面，以精确互补目标受体仍是计算蛋白质设计中的重大挑战。在本工作中，我们介绍了PepBridge，一种新的框架，用于联合设计蛋白质表面和结构，该框架无缝整合了受体表面几何形状和生化性质。从以3D点云表示的受体表面开始，PepBridge通过多步骤过程生成完整的蛋白质结构。首先，它利用去噪扩散桥模型（DDBMs）将受体表面映射到配体表面。接着，多模型扩散模型预测相应的结构，而Shape-Frame Matching Networks确保表面几何形状与主链架构的对齐。这种集成方法促进了表面互补性、构象稳定性以及化学可行性。在多种蛋白质设计场景中的广泛验证显示，PepBridge在生成结构上可行的蛋白质方面表现出色，代表了在自顶向下的蛋白质结构联合设计中的重要进展。
英文摘要：
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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