Ranking Peptide Binders by Affinity with AlphaFold**
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Abstract
AlphaFold has revolutionized structural biology by predicting highly accurate structures of proteins and their complexes with peptides and other proteins. However, for protein‐peptide systems, we are also interested in identifying the highest affinity binder among a set of candidate peptides. We present a novel competitive binding assay using AlphaFold to predict structures of the receptor in the presence of two peptides. For systems in which the individual structures of the peptides are well predicted, the assay captures the higher affinity binder in the bound state, and the other peptide in the unbound form with statistical significance. We test the application on six protein receptors for which we have experimental binding affinities to several peptides. We find that the assay is best suited for identifying medium to strong peptide binders that adopt stable secondary structures upon binding.
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- Authors
- Chang, L., & Perez, A.
- Affiliations
- University of Florida (US)
- Department of Chemistry University of Florida Gainesville FL USA
- Venue
- Angewandte Chemie International Edition
- Publisher
- Wiley
- Published
- 2023-01-12
- Volume
- 62
- Issue
- 7
- Pages
- e202213362-e202213362
- ISSN
- 1433-7851 (ISSN-L)
- 1521-3773
- OpenAlex
- W4312065672
- Cited by
- 100
- References
- 11
- Citations by year
- 2026: 16 · 2025: 27 · 2024: 25 · 2023: 21 · 2022: 11
- FWCI
- 6.86
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- Angewandte Chemie International Edition (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- American Cancer Society (AWD11297)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chemical Synthesis and Analysis
- Keywords
- peptide binding affinity, competitive binding assay, AlphaFold, protein-peptide complex, receptor binding, protein structure prediction, secondary structure stability
- MeSH terms
- Carrier Proteins, Peptides, Protein Binding, Proteins, Protein Structure, Secondary
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