A Unified View of “How Allostery Works”

• DOI: 10.1371/journal.pcbi.1003394
• Publication Date: 2014-02-06T21:46:55Z
• Authors: Chung-Jung Tsai; Ruth Nussinov
• Keywords: 0301 basic medicine; QH301-705.5; Computational Biology; Ligands; Models, Biological; 3. Good health; 03 medical and health sciences; Allosteric Regulation; Perspective; Thermodynamics; Biology (General); Allosteric Site; Signal Transduction

The question of how allostery works was posed almost 50 years ago. Since then it has been the focus much effort. This is for two reasons: first, intellectual curiosity basic science and desire to understand fundamental phenomena, second, its vast practical importance. Allostery at play in all processes living cell, increasingly drug discovery. Many models have successfully formulated, are able describe even absence a detailed structural mechanism. However, conceptual schemes designed qualitatively explain allosteric mechanisms usually lack quantitative mathematical model, unable link thermodynamic foundations. hampers insight into oncogenic mutations cancer progression biased agonists' actions. Here, we from three different standpoints: thermodynamics, free energy landscape population shift, structure; with exactly same descriptors. results unified view which not only clarifies elusive mechanism but also provides grasp agonist-mediated signaling pathways, guides Of note, reasons that coupling (or communication) does determine efficacy; however, communication channel what makes potential binding sites allosteric.