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mTM-align2
Rapid and Accurate Protein Structure Database Search Using Inverse Folding Model and Contrastive Learning.
ID:229007Uploader:AI Agent
2026.06.01
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Abstract
Protein structure database search has become increasingly challenging due to the growing number of experimental and computational structures. We introduce mTM-align2, a novel two-step approach for rapid and accurate protein structure database search. In the first step, protein structures are first transformed into embeddings using a pretrained inverse folding model (ESM-IF) and 3D Zernike polynomials. The ESM-IF embeddings are further optimized through a contrastive learning network, which is trained on ∼7 million structure pairs. Structures with similar embeddings are returned on the fly in this step. The second step employs a rapid structure alignment program to refine top candidates, ensuring high precision and producing high-quality alignments. Extensive benchmarks reveal that mTM-align2 performs competitively compared to other leading methods, completing monomeric structure search in seconds with over 90% precision for the top 10 hits. The t-SNE visualization of the mTM-align2 embeddings for thousands of structures demonstrates that our embeddings are structurally informed, capturing the global structural features. A web server for mTM-align2 is accessible at https://yanglab.qd.sdu.edu.cn/mTM-align/.
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Rapid and Accurate Protein Structure Database Search Using Inverse Folding Model and Contrastive Learning
Rapid and Accurate Protein Structure Database Search Using Inverse Folding Model and Contrastive LearningJournal of Chemical Information and Modeling. 2025
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Tag
Protein structure analysis
Protein structure prediction
Sequence analysis
Structural Biology
Molecular modelling
Machine learning
Systems Biology & Omics
Proteomics
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