scholarly journals Recent Advances and Applications of Molecular Docking to G Protein-Coupled Receptors

Molecules ◽  
2017 ◽  
Vol 22 (2) ◽  
pp. 340 ◽  
Author(s):  
Damian Bartuzi ◽  
Agnieszka Kaczor ◽  
Katarzyna Targowska-Duda ◽  
Dariusz Matosiuk
Keyword(s):  
Molecular Docking ◽  
G Protein ◽  
G Protein Coupled Receptors ◽  
Recent Advances ◽  
G Protein Coupled

Recent Advances of Small Molecular Regulators Targeting G Protein- Coupled Receptors Family for Oncology Immunotherapy

2019 ◽  
Vol 19 (16) ◽  
pp. 1464-1483 ◽  
Author(s):  
Peng He ◽  
Wenbo Zhou ◽  
Mingyao Liu ◽  
Yihua Chen
Keyword(s):  
G Protein ◽  
Cell Biology ◽  
Immune Cell ◽  
G Protein Coupled Receptors ◽  
Treatment Modalities ◽  
Immune Checkpoints ◽  
Considerable Proportion ◽  
Prostaglandin E ◽  
Recent Advances ◽  
G Protein Coupled

The great clinical success of chimeric antigen receptor T cell (CAR-T) and PD-1/PDL-1 inhibitor therapies suggests the drawing of a cancer immunotherapy age. However, a considerable proportion of cancer patients currently receive little benefit from these treatment modalities, indicating that multiple immunosuppressive mechanisms exist in the tumor microenvironment. In this review, we mainly discuss recent advances in small molecular regulators targeting G Protein-Coupled Receptors (GPCRs) that are associated with oncology immunomodulation, including chemokine receptors, purinergic receptors, prostaglandin E receptor EP4 and opioid receptors. Moreover, we outline how they affect tumor immunity and neoplasia by regulating immune cell recruitment and modulating tumor stromal cell biology. We also summarize the data from recent clinical advances in small molecular regulators targeting these GPCRs, in combination with immune checkpoints blockers, such as PD-1/PDL-1 and CTLA4 inhibitors, for cancer treatments.

scholarly journals Structure-Based Virtual Screening for Ligands of G Protein–Coupled Receptors: What Can Molecular Docking Do for You?

2021 ◽  
Vol 73 (4) ◽  
pp. 527-565
Author(s):  
Flavio Ballante ◽  
Albert J Kooistra ◽  
Stefanie Kampen ◽  
Chris de Graaf ◽  
Jens Carlsson
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
G Protein ◽  
G Protein Coupled Receptors ◽  
G Protein Coupled

Recent Advances in the Drug Discovery and Development of Dualsteric/ Bitopic Activators of G Protein-Coupled Receptors

2019 ◽  
Vol 19 (26) ◽  
pp. 2378-2392 ◽  
Author(s):  
Bethany A. Reinecke ◽  
Huiqun Wang ◽  
Yan Zhang
Keyword(s):  
G Protein ◽  
Binding Affinity ◽  
G Protein Coupled Receptors ◽  
Allosteric Modulator ◽  
High Binding ◽  
Subtype Selectivity ◽  
Recent Advances ◽  
Allosteric Sites ◽  
G Protein Coupled ◽  
High Binding Affinity

G protein-coupled receptors (GPCRs) represent the largest family of proteins targeted by drug design and discovery efforts. Of these efforts, the development of GPCR agonists is highly desirable, due to their therapeutic robust utility in treating diseases caused by deficient receptor signaling. One of the challenges in designing potent and selective GPCR agonists lies in the inability to achieve combined high binding affinity and subtype selectivity, due to the high homology between orthosteric sites among GPCR subtypes. To combat this difficulty, researchers have begun to explore the utility of targeting topographically distinct and less conserved binding sites, namely “allosteric” sites. Pursuing these sites offers the benefit of achieving high subtype selectivity, however, it also can result in a decreased binding affinity and potency as compared to orthosteric agonists. Therefore, bitopic ligands comprised of an orthosteric agonist and an allosteric modulator connected by a spacer and allowing binding with both the orthosteric and allosteric sites within one receptor, have been developed. It may combine the high subtype selectivity of an allosteric modulator with the high binding affinity of an orthosteric agonist and provides desired advantages over orthosteric agonists or allosteric modulators alone. Herein, we review the recent advances in the development of bitopic agonists/activators for various GPCR targets and their novel therapeutic potentials.

Anti-proliferative potential of cyclotetrapeptides from Bacillus velezensis RA5401 and their molecular docking on G-Protein-Coupled Receptors

2018 ◽  
Vol 123 ◽  
pp. 419-425 ◽  
Author(s):  
Najeeb Ur Rehman ◽  
Raeid M.M. Abed ◽  
Hidayat Hussain ◽  
Husain Yar Khan ◽  
Ajmal Khan ◽  
...  
Keyword(s):  
Molecular Docking ◽  
G Protein ◽  
G Protein Coupled Receptors ◽  
Proliferative Potential ◽  
Bacillus Velezensis ◽  
G Protein Coupled

scholarly journals Recent Advances on the Role of G Protein-Coupled Receptors in Hypoxia-Mediated Signaling

2016 ◽  
Vol 18 (2) ◽  
pp. 305-310 ◽  
Author(s):  
Rosamaria Lappano ◽  
Damiano Rigiracciolo ◽  
Paola De Marco ◽  
Silvia Avino ◽  
Anna Rita Cappello ◽  
...  
Keyword(s):  
G Protein ◽  
G Protein Coupled Receptors ◽  
Recent Advances ◽  
G Protein Coupled

scholarly journals Antibodies targeting G protein-coupled receptors: Recent advances and therapeutic challenges

mAbs ◽  
2017 ◽  
Vol 9 (5) ◽  
pp. 735-741 ◽  
Author(s):  
Mohammed Akli Ayoub ◽  
Pascale Crépieux ◽  
Markus Koglin ◽  
Marc Parmentier ◽  
Jean-Philippe Pin ◽  
...  
Keyword(s):  
G Protein ◽  
G Protein Coupled Receptors ◽  
Recent Advances ◽  
G Protein Coupled

scholarly journals Xiaoxuming Decoction Regulates Vascular Function by Modulating G Protein-Coupled Receptors: A Molecular Docking Study

2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Yanjia Shen ◽  
Ran Yang ◽  
Rui Zhou ◽  
Wendan Lu ◽  
Li Li ◽  
...  
Keyword(s):  
Molecular Docking ◽  
G Protein ◽  
Vascular Tone ◽  
G Protein Coupled Receptors ◽  
Regulatory Function ◽  
Network Pharmacology ◽  
Dependent Manner ◽  
Ang Ii ◽  
Urotensin Ii ◽  
G Protein Coupled

Xiaoxuming decoction (XXMD) is a traditional Chinese herbal medicine (CHM) that is used for the treatment of stroke in China. Stroke injury damages the cerebral vasculature and disrupts the autoregulation of vasoconstriction and vasodilatation, which is crucial for maintaining constant cerebral blood flow (CBF). It has been reported that XXMD exerts a positive effect on cerebral circulation in animal models of stroke. However, the mechanisms underlying the regulatory effect of XXMD on vascular tone, and the interactions among the multiple components of XXMD, remain unclear. In this study, XXMD was found to induce relaxation of the basilar artery rings of rats precontracted by 5-hydroxytryptamine (5-HT) in vitro, in a dose-dependent manner. The modulation of vascular tone and the process of cerebral ischemia are mediated via the interactions between G protein-coupled receptors (GPCRs) and their ligands, including 5-HT, angiotensin II (Ang II), and urotensin II (UII). Thus, the potential synergistic effects of the different components of XXMD on the regulation of vasoconstriction and vasodilation were further investigated by molecular docking based on network pharmacology. We constructed and analyzed a database comprising 963 compounds of XXMD and studied the interactions between five vascular GPCRs (5-HT1A receptor (5-HT1AR), 5-HT1B receptor (5-HT1BR), Ang II type 1 receptor (AT1R), beta 2-adrenergic receptor (β2-AR), and UII receptor (UTR)) and the various herbal constituents of XXMD using molecular docking. By constructing and analyzing the compound-target networks of XXMD, we found that Glycyrrhizae Radix et Rhizoma, Ginseng Radix et Rhizoma, and Paeoniae Radix Alba were the three major herbs that contained a large number of compounds with high docking scores. We additionally observed that several constituents of XXMD, including gallotannin, liquiritin apioside, nariutin, 1,2,3,4,6-pentagalloylglucose, folic acid, and ginsenoside Rb1, targeted multiple vascular GPCRs. Moreover, the interactions between the components of XXMD and the targets related to vascular tone constituted the comprehensive cerebrovascular regulatory function of XXMD and provided a material basis of the vasoregulatory function of XXMD. The study reports the contributions of various components of XXMD to the regulatory effects on vascular tone and provides scientific evidence for the multicomponent and multitargeting characteristics of XXMD.

Sign in / Sign up

Export Citation Format

Share Document