Discovering naturally occurring antifreeze peptides from microbiome by integrating protein language models and molecular dynamics simulation

Authors

• Ibrahim A. Imam, University of Kentucky
• Trevor Morey, University of Kentucky
• Yuexu Jiang, University of Kentucky
• Duolin Wang, University of Missouri
• Dong Xu, University of Missouri
• Qing Shao, University of KentuckyFollow

Abstract

Antifreeze peptides inhibit ice crystal growth and recrystallization, and are promising components of cryoprotective formulations for cell, tissue, and food preservation, as well as anti-icing surface coatings. However, the discovery of new antifreeze peptides has been hindered by their sequence diversity and the limited scalability of experimental screening. In this study, we identify novel antifreeze peptide candidates from a microbiome-derived sequence library using ensemble machine learning and molecular dynamics (MD) simulations. We developed an ensemble classifier composed of 10 adapter-tuned protein-language models and a random forest meta-learner. After training on a curated dataset of 73 766 sequences, we applied this ensemble to 56 008 amino acid sequences from an Arctic microbiome library to identify antifreeze peptide candidates. Structural prediction yields a diverse range of conformations for six selected candidates, including α-helices, coils, and combinations of both. To evaluate their functional relevance, atomistic MD simulations were conducted to assess conformational stability and solvent interactions under freezing conditions. One candidate shows persistent helicity, surface amphipathicity, and an organized hydration pattern consistent with structural signatures reported for ice-binding helices. These findings expand the known landscape of antifreeze peptides and highlight a scalable strategy for discovering functional peptides from complex biological sources.

Document Type

Article

Publication Date

2026

Notes/Citation Information

© The Royal Society of Chemistry 2026

Digital Object Identifier (DOI)

https://doi.org/10.1039/d5tb02758f

Funding Information

We acknowledge the National Institutes of Health (grant R01LM014510) for the financial support. D. W and D. X are also partially supported by the National Institutes of Health (grant R35GM126985). T. M and Q. S also acknowledge the support of the National Science Foundation (NO. 2150337). We also thank the University of Kentucky Center for Computational Sciences and Information Technology Services Research Computing for supporting and using associated research computing resources. This work also used Delta-GPU at NCSA through allocation CIS230053 from the Advanced Cyberinfrastructure Coordination Ecosystem: Services & Support (ACCESS) program, which National Science Foundation supports grants #2138259, #2138286, #2138307, #2137603, and #2138296.

Repository Citation

Imam, Ibrahim A.; Morey, Trevor; Jiang, Yuexu; Wang, Duolin; Xu, Dong; and Shao, Qing, "Discovering naturally occurring antifreeze peptides from microbiome by integrating protein language models and molecular dynamics simulation" (2026). Chemical and Materials Engineering Faculty Publications. 127.
https://uknowledge.uky.edu/cme_facpub/127