Dopamine D3 receptor antagonist reveals a cryptic pocket in aminergic GPCRs

• Published in: Scientific reports Vol. 8; no. 1; pp. 897 - 10
• Main Authors: Ferruz, Noelia, Doerr, Stefan, Vanase-Frawley, Michelle A., Zou, Yaozhong, Chen, Xiaomin, Marr, Eric S., Nelson, Robin T., Kormos, Bethany L., Wager, Travis T., Hou, Xinjun, Villalobos, Anabella, Sciabola, Simone, De Fabritiis, Gianni
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17.01.2018; Nature Publishing Group
• Subjects: 119/118; 631/154/309/606; 631/92/606; Animals; BASIC BIOLOGICAL SCIENCES; Binding Sites - physiology; Cell Line; Computational chemistry; Crystal structure; Crystallography, X-Ray - methods; Dopamine; Dopamine D3 receptor; Dopamine D3 receptors; Drug development; G protein-coupled receptors; Humanities and Social Sciences; Humans; Ligands; Macromolecules; Markov state models; Molecular Docking Simulation - methods; Molecular dynamics; Molecular Dynamics Simulation; multidisciplinary; Mutagenesis, Site-Directed - methods; Protein Binding - physiology; Protein structure; Receptors, Dopamine D3 - antagonists & inhibitors; Receptors, G-Protein-Coupled - chemistry; Receptors, G-Protein-Coupled - metabolism; Salicylamides - chemistry; Salicylamides - metabolism; Science; Science (multidisciplinary); Sf9 Cells; Site-directed mutagenesis

The recent increase in the number of X-ray crystal structures of G-protein coupled receptors (GPCRs) has been enabling for structure-based drug design (SBDD) efforts. These structures have revealed that GPCRs are highly dynamic macromolecules whose function is dependent on their intrinsic flexibilit...