Abstract
Protein optimization remains a longstanding goal in life sciences. Existing machine learning-assisted directed evolution (MLDE) methods primarily rely on sequence-only features, overlooking the critical spatial constraints and co-evolutionary interactions encoded in protein structures. However, directly integrating structural information remains challenging due to the scarcity of reliable mutant structures. To address these issues, we propose StructEvo, a novel structure-aware reinforcement learning framework for protein directed evolution. StructEvo employs a delta-structure fusion encoder to approximate mutant structure features via feature differences, enabling dynamic incorporation of spatial knowledge. The vast mutation space is then decomposed into manageable subspaces through a structure-aligned hierarchical action network, while a geometric constraint further stabilizes delta feature learning. Our approach outperforms prior state-of-the-art methods by 9.2% and 16.3% on two challenging optimization benchmarks, and further identifies an experimentally validated epistasis pattern in GFP, highlighting the importance of structural guidance for effective protein directed evolution.
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Publication details
- Journal
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- Open access
- Green open access
Cite this article
APA 7
Nie, Z., Zhao, S., Luo, Y., Fan, S., & Nie, Z. (2026). Structure-aware Reinforcement Learning for Protein Directed Evolution. https://omanscience.com/en/articles/structure-aware-reinforcement-learning-for-protein-directed-evolution
MLA 9
Nie, Zikun, et al. "Structure-aware Reinforcement Learning for Protein Directed Evolution." https://omanscience.com/en/articles/structure-aware-reinforcement-learning-for-protein-directed-evolution.
Chicago (author–date)
Nie, Zikun, Suyuan Zhao, Yizhen Luo, Siqi Fan, and Zaiqing Nie. 2026. "Structure-aware Reinforcement Learning for Protein Directed Evolution." https://omanscience.com/en/articles/structure-aware-reinforcement-learning-for-protein-directed-evolution.
Harvard
Nie, Z., Zhao, S., Luo, Y., Fan, S. and Nie, Z. (2026) 'Structure-aware Reinforcement Learning for Protein Directed Evolution', Available at: https://omanscience.com/en/articles/structure-aware-reinforcement-learning-for-protein-directed-evolution.
Vancouver
Nie Z, Zhao S, Luo Y, Fan S, Nie Z. Structure-aware Reinforcement Learning for Protein Directed Evolution. https://omanscience.com/en/articles/structure-aware-reinforcement-learning-for-protein-directed-evolution
IEEE
Z. Nie, S. Zhao, Y. Luo, S. Fan, and Z. Nie, "Structure-aware Reinforcement Learning for Protein Directed Evolution," https://omanscience.com/en/articles/structure-aware-reinforcement-learning-for-protein-directed-evolution.