A Unified View of “How Allostery Works”
By Chung-Jung Tsai, Ruth Nussinov. PLoS Comput. Biol., 2014
369 citations recorded by the source corpus.
The question of how allostery works was posed almost 50 years ago. Since then it has been the focus of much effort. This is for two reasons: first, the intellectual curiosity of basic science and the desire to understand fundamental phenomena, and second, its vast practical importance. Allostery is at play in all processes in the living cell, and increasingly in drug discovery. Many models have been successfully formulated, and are able to describe allostery even in the absence of a detailed structural mechanism. However, conceptual schemes designed to qualitatively explain allosteric mechanisms usually lack a quantitative mathematical model, and are unable to link its thermodynamic and structural foundations. This hampers insight into oncogenic mutations in cancer progression and biased agonists' actions. Here, we describe how allostery works from three different standpoints: thermodynamics, free energy landscape of population shift, and structure; all with exactly the same allosteric descriptors. This results in a unified view which not only clarifies the elusive allosteric mechanism but also provides structural grasp of agonist-mediated signaling pathways, and guides allosteric drug discovery. Of note, the unified view reasons that allosteric coupling (or communication) does not determine the allosteric efficacy; however, a communication channel is what makes potential binding sites allosteric.
Subfields: Computational Theory and Mathematics, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/d5f164e1507b862edc8990fbd781119f4b7932c8
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In Computational Theory and Mathematics
- Holger Flechsig
- Dima Kozakov
- Le Yan
- Matthieu Wyart
- Carolina Brito
- Riccardo Ravasio
- James Andrew McCammon
- Ruth Nussinov
In Molecular Biology
- Matthieu Wyart
- Carolina Brito
- Riccardo Ravasio
- Dima Kozakov
- Holger Flechsig
- John Karanicolas
- Le Yan
- Chung-Jung Tsai
Citations in the corpus
- Design of Elastic Networks with Evolutionary Optimized Long-Range Communication as Mechanical Models of Allosteric Proteins (2017, background): “jp [1] Tsai C-J, Nussinov R (2014) A unified view of “how allostery works”.”
- Allostery in Its Many Disguises: From Theory to Applications (2019, background): “Nussinov, R., and Tsai, C.J. (2015).”