TY - JOUR
T1 - Recent Advances in Structure-Based Drug Design Targeting Class A G Protein-Coupled Receptors Utilizing Crystal Structures and Computational Simulations
AU - Lee, Yoonji
AU - Basith, Shaherin
AU - Choi, Sun
N1 - Publisher Copyright:
© 2017 American Chemical Society.
PY - 2018/1/11
Y1 - 2018/1/11
N2 - G protein-coupled receptors (GPCRs) represent the largest and most physiologically important integral membrane protein family, and these receptors respond to a wide variety of physiological and environmental stimuli. GPCRs are among the most critical therapeutic targets for numerous human diseases, and approximately one-third of the currently marketed drugs target this receptor family. The recent breakthroughs in GPCR structural biology have significantly contributed to our understanding of GPCR function, ligand binding, and pharmacological action as well as to the design of new drugs. This perspective highlights the latest advances in GPCR structures with a focus on the receptor-ligand interactions of each receptor family in class A nonrhodopsin GPCRs as well as the structural features for their activation, biased signaling, and allosteric mechanisms. The current state-of-the-art methodologies of structure-based drug design (SBDD) approaches in the GPCR research field are also discussed.
AB - G protein-coupled receptors (GPCRs) represent the largest and most physiologically important integral membrane protein family, and these receptors respond to a wide variety of physiological and environmental stimuli. GPCRs are among the most critical therapeutic targets for numerous human diseases, and approximately one-third of the currently marketed drugs target this receptor family. The recent breakthroughs in GPCR structural biology have significantly contributed to our understanding of GPCR function, ligand binding, and pharmacological action as well as to the design of new drugs. This perspective highlights the latest advances in GPCR structures with a focus on the receptor-ligand interactions of each receptor family in class A nonrhodopsin GPCRs as well as the structural features for their activation, biased signaling, and allosteric mechanisms. The current state-of-the-art methodologies of structure-based drug design (SBDD) approaches in the GPCR research field are also discussed.
UR - http://www.scopus.com/inward/record.url?scp=85041612964&partnerID=8YFLogxK
U2 - 10.1021/acs.jmedchem.6b01453
DO - 10.1021/acs.jmedchem.6b01453
M3 - Review article
C2 - 28657745
AN - SCOPUS:85041612964
SN - 0022-2623
VL - 61
SP - 1
EP - 46
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 1
ER -