提出RIGA-Fold框架,提升蛋白质逆折叠的序列与结构一致性。
RIGA-Fold: A General Framework for Protein Inverse Folding via Recurrent Interaction and Geometric Awareness
- 用循环交互和几何感知机制捕捉长程依赖关系。
- 在多个基准上优于当前最优模型,序列恢复率更高。
- 适合蛋白质设计、药物研发等生物计算领域研究者。
蛋白质逆折叠任务旨在为给定结构预测氨基酸序列,对从头蛋白设计至关重要。现有基于图神经网络的方法通常受限于感受野不足,难以捕捉长程依赖,且采用单次推理模式导致误差累积。为此,我们提出RIGA-Fold框架,融合循环交互与几何感知机制。微观层面引入几何注意力更新模块(GAU),使边特征显式作为注意力键,实现严格SE(3)不变的局部编码;宏观层面设计基于注意力的全局上下文桥,动态注入全局拓扑信息。为弥合结构与序列模态差距,提出增强版RIGA-Fold*,通过双流架构整合可训练几何特征与冻结的进化先验(来自ESM-2和ESM-IF)。最后,采用类生物学的“预测-回溯-精炼”策略迭代去噪序列分布。在CATH 4.2、TS50和TS500基准上的大量实验表明,该几何框架具有强竞争力,而RIGA-Fold*在序列恢复和结构一致性方面显著优于现有最优方法。
原文摘要 · Abstract (English)
Protein inverse folding, the task of predicting amino acid sequences for desired structures, is pivotal for de novo protein design. However, existing GNN-based methods typically suffer from restricted receptive fields that miss long-range dependencies and a "single-pass" inference paradigm that leads to error accumulation. To address these bottlenecks, we propose RIGA-Fold, a framework that synergizes Recurrent Interaction with Geometric Awareness. At the micro-level, we introduce a Geometric Attention Update (GAU) module where edge features explicitly serve as attention keys, ensuring strictly SE(3)-invariant local encoding. At the macro-level, we design an attention-based Global Context Bridge that acts as a soft gating mechanism to dynamically inject global topological information. Furthermore, to bridge the gap between structural and sequence modalities, we introduce an enhanced variant, RIGA-Fold*, which integrates trainable geometric features with frozen evolutionary priors from ESM-2 and ESM-IF via a dual-stream architecture. Finally, a biologically inspired ``predict-recycle-refine'' strategy is implemented to iteratively denoise sequence distributions. Extensive experiments on CATH 4.2, TS50, and TS500 benchmarks demonstrate that our geometric framework is highly competitive, while RIGA-Fold* significantly outperforms state-of-the-art baselines in both sequence recovery and structural consistency.
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