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CycleDesigner: Leveraging CycRFdiffusion and HighFold to Design Cyclic Peptide Binders for Specific Targets
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Abstract
Cyclic peptides are potentially therapeutic in clinical applications, due to their great stability and activity. Yet, designing and identifying potential cyclic peptide binders targeting specific targets remains a formidable challenge, entailing significant time and resources. In this study, we modified the powerful RFdiffusion model to allow the cyclic peptide structure identification (CycRFdiffusion) and integrated it with ProteinMPNN and HighFold to design binders for specific targets. This innovative approach, termed CycleDesigner, was followed by a series of scoring functions for efficient filtering. With the combination of effective cyclic peptide design and filtering, our study aims to further broaden the scope of cyclic peptide binder design.
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Metadata
- Authors
- Zhang, C., Xu, Z., Lin, K., Zhu, N., Zhang, C., Xu, W., Guo, J., Su, A., Li, C., & Duan, H.
- Affiliations
- Zhejiang University of Technology (CN)
- AI Department
- Macao Polytechnic University (MO)
- Zhejiang University (CN)
- Corresponding author
- Duan, Hongliang
- Venue
- Journal of Chemical Information and Modeling
- Publisher
- American Chemical Society (ACS)
- Published
- 2025-06-10
- Volume
- 65
- Issue
- 12
- Pages
- 6155-6165
- ISSN
- 1549-9596 (ISSN-L)
- 1549-960X
- OpenAlex
- W4411210758
- Cited by
- 12
- References
- 40
- Citations by year
- 2026: 9 · 2025: 3
- FWCI
- 3.61
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- Journal of Chemical Information and Modeling (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- Natural Science Foundation of Zhejiang Province (LD22H300004)
- Topics
- Physical Sciences › Chemistry › Organic Chemistry › Chemical Synthesis and Analysis
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Drug Discovery › Computational Drug Discovery Methods
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- cyclic peptides, RFdiffusion, ProteinMPNN, scoring functions
- MeSH terms
- Models, Molecular, Peptides, Cyclic, Protein Binding, Drug Design
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