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Current Medicinal Chemistry

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ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

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Review Article

GPCR Allostery: A View from Computational Biology

Author(s): Mengrong Li, Yiqiong Bao, Miaomiao Li and Jingjing Guo*

Volume 30, Issue 40, 2023

Published on: 16 February, 2023

Page: [4533 - 4553] Pages: 21

DOI: 10.2174/0929867330666230113125246

Price: $65

Abstract

G protein-coupled receptors (GPCRs) represent a large superfamily of cell-surface proteins that mediate cell signaling and regulate virtually various aspects of physiological and pathological processes, therefore serving as a rich source of drug targets. As intrinsically allosteric proteins, numerous functions of GPCRs are regulated via allostery, whereby allosteric modulators binding at a distal site regulate the function of the typical orthosteric site. However, only a few GPCR allosteric ligands have been presently approved as drugs due to the high dynamic structures of GPCRs. Fortunately, the rapid development of computational biology sheds light on understanding the mechanism of GPCR allosteric ligands, which is critical for the discovery of new therapeutic agents. Here, we present a comprehensive overview of the currently available resources and approaches in computational biology related to G protein-coupled receptor allostery and their conformational dynamics. In addition, current limitations and major challenges in the field are also discussed accordingly.

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