arXiv:2608.29207cs.AIcs.LG2026-08

提出超图建模方法,突破蛋白质结构模型表达极限。

Hyper-Fold: Exploring the Expressive Limit of Sequence-Geometry Learning for Proteins via Hypergraph Modeling

论文配图:Hyper-Fold: Exploring the Expressive Limit of Sequence-Geometry Learning for Proteins via Hypergraph Modeling
图 1 · 摘自论文原文
  • 用超图结构分离序列与几何信息,实现高阶交互建模。
  • 在酶功能预测等任务中超越现有模型,参数量少68倍、延迟降4.8倍。
  • 无需语言模型特征,适合轻量化3D蛋白结构分析场景。

蛋白质结构建模依赖于残基序列内容与三维几何位置之间的相互作用。本文揭示:所有二阶交互的充分统计量——内容-几何外积上的完整双线性算子——是该类模型的表达上限,而主流几何图神经网络的加性消息传递机制无法捕捉内容-几何耦合。为此提出Hyper-Fold,一种秩-K可分离卷积主干,以消息传递代价逼近表达上限:每个局部邻域被组织为序列超边和接触超边,由边条件矩阵调节,其系数由几何生成,基函数通过K个学习得到。在酶功能预测、折叠分类和配体结合位点检测任务中,Hyper-Fold及其分层变体Hyper-Fold-Deep均优于现有蛋白质专用结构编码器;其中,Hyper-Fold-Pocket(锚定集合预测头)在UniSite-DS及两个零样本基准上超越UniSite-3D,无需序列语言模型特征,参数量减少68倍,延迟降低4.8倍,表明足够表达力的3D主干可恢复融合架构此前从演化规模预训练中借用的信息。

原文摘要 · Abstract (English)

Protein structure modeling rests on a single computational primitive: the interaction between what a residue is (sequence content) and where it sits (three-dimensional geometry). What is the expressive limit of this layer class? We show that the complete bilinear operator over content-geometry outer products--the sufficient statistic of all second-order interactions--is the expressive ceiling, while the additive message passing of mainstream geometric GNNs is provably blind to content-geometry binding. We then introduce Hyper-Fold, a rank-K separable convolutional backbone approaching this ceiling at message-passing cost: each radius neighborhood is organized into a sequence hyperedge and a contact hyperedge, modulated by an edge-conditioned matrix-valued operator factorized into K learned basis operators with geometry-generated coefficients. Across enzyme function prediction, fold classification, and ligand binding site detection, Hyper-Fold and its hierarchical variant Hyper-Fold-Deep achieve the best results among protein-specific structure encoders; Hyper-Fold-Pocket, an anchored set-prediction head, surpasses UniSite-3D on UniSite-DS and two zero-shot benchmarks with no sequence language model features, 68x fewer parameters, and 4.8x lower latency--suggesting that a sufficiently expressive 3D backbone recovers information that fusion architectures previously borrowed from evolution-scale pretraining.

蛋白质结构超图建模3D深度学习轻量化

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