arXiv:2507.10877physics.chem-phcs.LG2025-07被引 1

BioScore统一评估多种生物分子复合物结构,性能显著优于现有方法。

BioScore: A Foundational Scoring Function For Diverse Biomolecular Complexes

  • 采用双尺度几何图网络,融合结构评估与亲和力预测模块。
  • 在16个基准上超越70种传统与深度学习方法,最高提升90%相关性。
  • 适用于零样本/少样本预测,特别擅长环肽等复杂系统建模。

生物分子复合物的结构评估对解析分子模型的功能意义至关重要,有助于理解生物学机制并推动药物发现。然而,现有基于结构的评分函数在跨不同生物系统时泛化能力不足。本文提出BioScore,一种基础性评分函数,通过双尺度几何图学习框架,解决数据稀疏、跨系统表征和任务兼容性三大挑战,并针对结构评估与亲和力预测设计专用模块。BioScore支持亲和力预测、构象排序和基于结构的虚拟筛选等多种任务。在涵盖蛋白质、核酸、小分子和碳水化合物的16个基准上,其表现持续优于或匹配70种传统与深度学习方法。新提出的PPI基准可全面评估蛋白-蛋白复合物评分性能。BioScore展现出广泛适用性:(1)混合结构预训练使蛋白-蛋白亲和力预测提升达40%,抗原-抗体结合相关性提高超过90%;(2)跨系统泛化能力实现零样本与少样本预测,相关性最高提升71%;(3)统一表示可捕捉化学复杂系统如环肽,亲和力预测提升超60%。BioScore建立了跨复杂生物分子场景的鲁棒且通用的结构评估框架。

原文摘要 · Abstract (English)

Structural assessment of biomolecular complexes is vital for translating molecular models into functional insights, shaping our understanding of biology and aiding drug discovery. However, current structure-based scoring functions often lack generalizability across diverse biomolecular systems. We present BioScore, a foundational scoring function that addresses key challenges -- data sparsity, cross-system representation, and task compatibility -- through a dual-scale geometric graph learning framework with tailored modules for structure assessment and affinity prediction. BioScore supports a wide range of tasks, including affinity prediction, conformation ranking, and structure-based virtual screening. Evaluated on 16 benchmarks spanning proteins, nucleic acids, small molecules, and carbohydrates, BioScore consistently outperforms or matches 70 traditional and deep learning methods. Our newly proposed PPI Benchmark further enables comprehensive evaluation of protein-protein complex scoring. BioScore demonstrates broad applicability: (1) pretraining on mixed-structure data boosts protein-protein affinity prediction by up to 40% and antigen-antibody binding correlation by over 90%; (2) cross-system generalizability enables zero- and few-shot prediction with up to 71% correlation gain; and (3) its unified representation captures chemically challenging systems such as cyclic peptides, improving affinity prediction by over 60%. BioScore establishes a robust and generalizable framework for structural assessment across complex biomolecular landscapes.

分子评分结构预测生物分子图神经网络

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