AlphaFold2 Can Predict Single-Mutation Effects
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Abstract
AlphaFold2 (AF) is a promising tool, but is it accurate enough to predict single mutation effects? Here, we report that the localized structural deformation between protein pairs differing by only 1-3 mutations-as measured by the effective strain-is correlated across 3901 experimental and AF-predicted structures. Furthermore, analysis of ∼11 000 proteins shows that the local structural change correlates with various phenotypic changes. These findings suggest that AF can predict the range and magnitude of single-mutation effects on average, and we propose a method to improve precision of AF predictions and to indicate when predictions are unreliable.
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- Authors
- McBride, J. M., Polev, K., Abdirasulov, A., Reinharz, V., Grzybowski, B. A., & Tlusty, T.
- Affiliations
- Institute for Basic Science (KR)
- Ulsan National Institute of Science and Technology (KR)
- Université du Québec à Montréal (CA)
- Corresponding author
- Tlusty, Tsvi
- Venue
- Physical Review Letters
- Publisher
- American Physical Society (APS)
- Published
- 2023-11-20
- Volume
- 131
- Issue
- 21
- Pages
- 218401-218401
- ISSN
- 0031-9007 (ISSN-L)
- 1079-7114
- OpenAlex
- W4388825176
- Cited by
- 87
- References
- 7
- Citations by year
- 2026: 15 · 2025: 34 · 2024: 28 · 2023: 7 · 2022: 3
- FWCI
- 7.47
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- Physical Review Letters (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- arXiv (Cornell University) (submittedVersion)
- arXiv (Cornell University)
- Funders
- Institute for Basic Science (IBS-R020-D1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Machine Learning in Bioinformatics
- Keywords
- AlphaFold2, protein structure prediction, equivalent strain, structural deformation, phenotypic change, forecast reliability
- MeSH terms
- Mutation, Proteins, Software
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