50 years of allosteric interactions: the twists and turns of the models

The concept of allosteric interactions between topographically distinct sites, and the subsequent Monod-Wyman-Changeux model proposed in 1965 for the conformational change mediating them, arose around 50 years ago. Many classic regulatory proteins follow this model, which has been expanded and challenged over the years. The concept of indirect or 'allosteric' interaction between topographically distinct sites, and the subsequent 1965 Monod-Wyman-Changeux (MWC) model for the conformational change mediating them, arose around 50 years ago. Many classic regulatory proteins (including haemoglobin, Asp transcarbamylase and nicotinic acetylcholine receptor) follow the central paradigm of the MWC model, which has been expanded and challenged as a result of novel technologies. Importantly, the concept of allosteric interaction has aided our understanding of human diseases and drug design.