TY - JOUR
T1 - GPCR Allostery
T2 - A View from Computational Biology
AU - Li, Mengrong
AU - Bao, Yiqiong
AU - Li, Miaomiao
AU - Guo, Jingjing
N1 - Publisher Copyright:
© 2023 Bentham Science Publishers.
PY - 2023
Y1 - 2023
N2 - G protein-coupled receptors (GPCRs) represent a large superfamily of cell-sur-face 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 ap-proved 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.
AB - G protein-coupled receptors (GPCRs) represent a large superfamily of cell-sur-face 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 ap-proved 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.
KW - G protein-coupled receptors
KW - allosteric modulators
KW - allostery
KW - computational biology
KW - conformational dynamics
KW - molecular dynamics simulation
UR - http://www.scopus.com/inward/record.url?scp=85162745972&partnerID=8YFLogxK
U2 - 10.2174/0929867330666230113125246
DO - 10.2174/0929867330666230113125246
M3 - Review article
C2 - 36642879
AN - SCOPUS:85162745972
SN - 0929-8673
VL - 30
SP - 4533
EP - 4553
JO - Current Medicinal Chemistry
JF - Current Medicinal Chemistry
IS - 40
ER -