RIGA-Fold: A General Framework for Protein Inverse Folding via Recurrent Interaction and Geometric Awareness
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Abstract (arXiv)
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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References · 11
- 2018Deeper Insights into Graph Convolutional Networks for Semi-Supervised Learningcited by 1,099
- 2020On the Bottleneck of Graph Neural Networks and its Practical Implicationscited by 624
- 2020SE(3)-Transformers: 3D Roto-Translation Equivariant Attention Networkscited by 602
- 2019DeepGCNs: Can GCNs Go as Deep as CNNs?cited by 527
- 2020Learning from Protein Structure with Geometric Vector Perceptronscited by 308
- 2022PiFold: Toward effective and efficient protein inverse foldingcited by 82
- 2023Structure-informed Language Models Are Protein Designerscited by 68
- 2019Learning protein sequence embeddings using information from structurecited by 50
- 2022AlphaDesign: A graph protein design method and benchmark on AlphaFoldDBcited by 39
- 2023De novo protein design using geometric vector field networkscited by 14
- 2022A Survey on Protein Representation Learning: Retrospect and Prospectcited by 10
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