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.
CITATION STYLE
Song, K., & Zhang, J. (2018). Single Binding Pockets Versus Allosteric Binding. In Methods in Molecular Biology (Vol. 1825, pp. 295–326). Humana Press Inc. https://doi.org/10.1007/978-1-4939-8639-2_9
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