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Research citation

Cyclic peptide structure prediction and design using AlphaFold2.

ComputationalLow Moderate evidence

This record provides bibliographic details and links to the original research. An editorial study breakdown is not available.

What the researchers found

AlphaFold2 was adapted to predict and design cyclic peptide structures. Over 10,000 designs were generated, with 8 tested sequences matching predictions closely and some binding targets with nanomolar affinity.

Why it matters

Designing cyclic peptides has been limited by lack of deep learning tools. This method enables rapid computational design of therapeutic peptide candidates.

The numbers in context

Over 10,000 designs. 8 tested matched X-ray structures (RMSD under 1 angstrom). IC50 under 50 nM against MDM2 and Keap1.

How the study worked

Deep learning approach adapting AlphaFold2 for cyclic peptides. Structure prediction, sequence redesign, and de novo hallucination. X-ray crystallography and binding assay validation.

Who was studied

Computationally designed cyclic peptides

What this study cannot tell us

Only 8 of 10,000+ designs experimentally tested. Two targets only. In vitro binding does not guarantee in vivo efficacy.

Read the original research

Cyclic peptide structure prediction and design using AlphaFold2.

Nature communications, 16(1), 4730

Citation

Rettie, Stephen A; Campbell, Katelyn V; Bera, Asim K; Kang, Alex; Kozlov, Simon; Bueso, Yensi Flores; De La Cruz, Joshmyn; Ahlrichs, Maggie; Cheng, Suna; Gerben, Stacey R; Lamb, Mila; Murray, Analisa; Adebomi, Victor; Zhou, Guangfeng; DiMaio, Frank; Ovchinnikov, Sergey; Bhardwaj, Gaurav. (2025). Cyclic peptide structure prediction and design using AlphaFold2.. Nature communications, 16(1), 4730. https://doi.org/10.1038/s41467-025-59940-7