Allostery: An Overview of Its History, Concepts, Methods, and Applications
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The concept of allostery has evolved in the past century. In this Editorial, we briefly overview the history of allostery, from the pre-allostery nomenclature era starting with the Bohr effect (1904) to the birth of allostery by Monod and Jacob (1961). We describe the evolution of the allostery concept, from a conformational change in a two-state model (1965, 1966) to dynamic allostery in the ensemble model (1999); from multi-subunit (1965) proteins to all proteins (2004). We highlight the current available methods to study allostery and their applications in studies of conformational mechanisms, disease, and allosteric drug discovery. We outline the challenges and future directions that we foresee. Altogether, this Editorial narrates the history of this fundamental concept in the life sciences, its significance, methodologies to detect and predict it, and its application in a broad range of living systems.
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AlphaFold, which predicts single ranked structures for a protein sequence, is unable to address directly allosteric mechanisms, which are based on populations of conformational states in ensembles.
“AlphaFold, which predicts single ranked structures for a protein sequence, is unable to address directly allosteric mechanisms, which are based on the populations of conformational states in the ensembles.”
From AlphaFold, Artificial Intelligence (AI), and Allostery (2022) · cites this paper as [106]
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References 28 · Cited by 281
- Authors
- Liu, J., & Nussinov, R.
- Affiliations
- University of North Texas (US)
- Tel Aviv University (IL)
- Corresponding author
- Liu, Jin
- Nussinov, Ruth
- Venue
- PLOS Computational Biology
- Publisher
- Public Library of Science (PLoS)
- Published
- 2016-06-02
- Volume
- 12
- Issue
- 6
- Pages
- e1004966
- ISSN
- 1553-734X (ISSN-L)
- 1553-7358
- PMC
- PMC4890769
- OpenAlex
- W2417513559
- Cited by
- 281
- References
- 28
- Citations by year
- 2026: 19 · 2025: 33 · 2024: 31 · 2023: 49 · 2022: 30 · 2021: 28 · 2020: 25 · 2019: 29 · 2018: 20 · 2017: 12 · 2016: 3 · 2012: 1
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS Computational Biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
- Keywords
- allosteric regulation, Bohr effect, two-state model, dynamic allostery, ensemble learning, protein conformational change, allosteric drug discovery
- MeSH terms
- Allosteric Regulation, Biochemistry, Humans, Models, Biological, Biomedical Research, History, 20th Century, History, 21st Century
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