Enhancing Protein Mutation Effect Prediction through a Retrieval-Augmented Framework
Ruihan Guo, Rui Wang, Ruidong Wu, Zhizhou Ren, Jiahan Li, Shitong Luo, Zuofan Wu, Qiang Liu, Jian Peng, Jianzhu Ma
Abstract
Predicting the effects of protein mutations is crucial for analyzing protein functions and understanding genetic diseases. However, existing models struggle to effectively extract mutation-related local structure motifs from protein databases, which hinders their predictive accuracy and robustness. To tackle this problem, we design a novel retrieval-augmented framework for incorporating similar structure information in known protein structures. We create a vector database consisting of local structure motif embeddings from a pre-trained protein structure encoder, which allows for efficient retrieval of similar local structure motifs during mutation effect prediction. Our findings demonstrate that leveraging this method results in the SOTA performance across multiple protein mutation prediction datasets, and offers a scalable solution for studying mutation effects.
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Cited by top-tier papers4
- Accurately Predicting Protein Mutational Effects via a Hierarchical Many-Body Attention NetworkDahao Xu, Jiahua Rao, Mingming Zhu, Jixian Zhang et al.NeurIPS 2025 · 4 citations
- Multimodal Mixture-of-Experts with Retrieval Augmentation for Protein Active Site IdentificationJiayang Wu, Jiale Zhou, Rubo Wang, Xingyi Zhang et al.AAAI 2026
- MutAtlas: A PDB-Wide Energy-Guided Atlas of Protein Mutation EffectsRuihan Guo, Chaoran Cheng, Zhanghan Ni, Neil He et al.ICML 2026
- Hotspot-Driven Peptide Design via Multi-Fragment Autoregressive ExtensionJiahan Li, Tong Chen, Shitong Luo, Chaoran Cheng et al.ICLR 2025
Builds on10
- Language models enable zero-shot prediction of the effects of mutations on protein functionJoshua Meier, Roshan Rao, Robert Verkuil, Jason Liu et al.NeurIPS 2021 · 969 citations
- MSA TransformerRoshan Rao, Jason Liu, Robert Verkuil, Joshua Meier et al.ICML 2021 · 686 citations
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- Tranception: Protein Fitness Prediction with Autoregressive Transformers and Inference-time RetrievalPascal Notin, Mafalda Dias, Jonathan Frazer, Javier Marchena-Hurtado et al.ICML 2022 · 236 citations
- Memorizing TransformersYuhuai Wu, Markus Norman Rabe, DeLesley Hutchins, Christian SzegedyICLR 2022 · 231 citations
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