Single Binding Pockets Versus Allosteric Binding

  • Kun Song
  • Jian ZhangEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1825)


An orthosteric site is commonly viewed as the primary, functionally binding pocket on a receptor. Signal molecules, endogenous agonists, and substrates are recognized by and bind to the orthosteric site of a specific target, resulting in a biological effect. A malfunctioning active site on a crucial receptor has been confirmed as the culprit that causes many metabolic disturbances, neurologic disorders, and genetic diseases. A competitive inhibitor that has a stronger binding affinity can outcompete an orthosteric ligand. An allosteric site, which is nonoverlapping and topographically distinct from the active pocket, can emerge as a potential regulatory site on the protein surface. An allosteric modulator interacts with a specific binding site, affecting the atoms of nearby residues, thus eliciting a series of conformational changes in the residues at the active site through propagation pathways. Allosteric regulation can potentiate or inhibit function instead of blocking it, and this is a promising strategy for drug design. In this chapter, we describe the tools and protocols for allosteric site analysis and allosteric ligand design.

Key words

Allostery Allosteric site Orthosteric site Drug design Computational methods 


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Ministry of EducationShanghai Jiao-Tong University School of MedicineShanghaiChina

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