Consensus protein design
Open accessAbstract
A popular and successful strategy in semi-rational design of protein stability is the use of evolutionary information encapsulated in homologous protein sequences. Consensus design is based on the hypothesis that at a given position, the respective consensus amino acid contributes more than average to the stability of the protein than non-conserved amino acids. Here, we review the consensus design approach, its theoretical underpinnings, successes, limitations and challenges, as well as providing a detailed guide to its application in protein engineering.
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Consensus sequences determined by multiple sequence alignment are believed to play a crucial part in maintaining protein stability and adhesion throughout evolution.
“We then performed multiple sequence alignment using Clustal Omega23 to determine consensus sequences for each species (Extended Data Fig. 1), which are believed to play a crucial part in maintaining protein stability and adhesion throughout evolution24,25.”
From Data-driven de novo design of super-adhesive hydrogels (2025) · cites this paper as [24]
The Introduction describes deriving consensus sequences from multiple sequence alignments, and ‘Engineering thermodynamic stability’ explains why conserved residues are more likely to stabilize proteins. Our copy does not support the attributed role in adhesion; it also notes that some conserved residues are neutral or destabilizing. (LLM, conf=0.88)
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Low-N protein engineering with data-efficient deep learning
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- Authors
- Porebski, B. T., & Buckle, A. M.
- Affiliations
- MRC Laboratory of Molecular Biology (GB)
- Monash University (AU)
- Corresponding author
- Buckle, Ashley M.
- Venue
- Protein Engineering Design and Selection
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-06-05
- Volume
- 29
- Issue
- 7
- Pages
- 245-251
- ISSN
- 0269-2139 (ISSN-L)
- 1741-0126
- 1741-0134
- PMC
- PMC4917058
- OpenAlex
- W2412714128
- Cited by
- 215
- References
- 110
- Citations by year
- 2026: 21 · 2025: 25 · 2024: 26 · 2023: 25 · 2022: 29 · 2021: 27 · 2020: 16 · 2019: 16 · 2018: 15 · 2017: 10 · 2016: 5
- FWCI
- 1.42
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Protein Engineering Design and Selection (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- National Health and Medical Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein purification and stability
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Enzyme Catalysis and Immobilization
- Keywords
- consensus design, protein stability, homologous protein sequences, evolutionary information, amino acid conservation, protein engineering
- MeSH terms
- Amino Acid Sequence, Animals, Humans, Proteins, Temperature, Thermodynamics, Protein Engineering, Sequence Alignment, Informatics, Protein Stability
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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