Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

G Protein-coupled Receptors01:15

G Protein-coupled Receptors

19.3K
G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
19.3K
Ligand Binding Sites02:40

Ligand Binding Sites

15.7K
Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
15.7K
GPCR Desensitization01:12

GPCR Desensitization

8.6K
G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
8.6K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Synthesis of 1,3-Disubstituted 3-Azabicyclo[3.2.0]heptane Libraries for Fragment-Based Drug Discovery.

Organic letters·2026
Same author

ANNalog: generation of MedChem-similar molecules.

Journal of cheminformatics·2026
Same author

Leveraging fragment-based drug discovery to advance 3D scaffolds into potent ligands: application to the histamine H<sub>1</sub> receptor.

RSC medicinal chemistry·2026
Same author

Optical control of H<sub>1</sub> receptor signaling with a BODIPY-photocaged antihistamine.

Biochemical pharmacology·2026
Same author

Correction to "Fragment-to-Lead Medicinal Chemistry Publications in 2024: A Tenth Annual Perspective".

Journal of medicinal chemistry·2026
Same author

Inhibition of constitutive activity of the atypical chemokine receptor 3 by the small-molecule inverse agonist VUF16840.

Molecular pharmacology·2025

Related Experiment Video

Updated: Mar 19, 2026

Parallel Interrogation of &#946;-Arrestin2 Recruitment for Ligand Screening on a GPCR-Wide Scale using PRESTO-Tango Assay
09:03

Parallel Interrogation of β-Arrestin2 Recruitment for Ligand Screening on a GPCR-Wide Scale using PRESTO-Tango Assay

Published on: March 10, 2020

14.0K

Function-specific virtual screening for GPCR ligands using a combined scoring method.

Albert J Kooistra1, Henry F Vischer1, Daniel McNaught-Flores1

  • 1Amsterdam Institute for Molecules, Medicines and Systems (AIMMS), Division of Medicinal Chemistry, Faculty of Sciences, Vrije Universiteit Amsterdam, De Boelelaan 1108, 1081 HZ Amsterdam, The Netherlands.

Scientific Reports
|June 25, 2016
PubMed
Summary

A new virtual screening method combines scoring functions and molecular interaction fingerprints to discover novel drug ligands for G protein-coupled receptors (GPCRs). This approach successfully identified potent histamine H1 receptor antagonists and selective beta2-adrenoceptor agonists.

More Related Videos

A "Dual-Addition" Calcium Fluorescence Assay for the High-Throughput Screening of Recombinant G Protein-Coupled Receptors
08:46

A "Dual-Addition" Calcium Fluorescence Assay for the High-Throughput Screening of Recombinant G Protein-Coupled Receptors

Published on: December 2, 2022

2.9K
Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
10:29

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors

Published on: May 9, 2025

2.6K

Related Experiment Videos

Last Updated: Mar 19, 2026

Parallel Interrogation of &#946;-Arrestin2 Recruitment for Ligand Screening on a GPCR-Wide Scale using PRESTO-Tango Assay
09:03

Parallel Interrogation of β-Arrestin2 Recruitment for Ligand Screening on a GPCR-Wide Scale using PRESTO-Tango Assay

Published on: March 10, 2020

14.0K
A "Dual-Addition" Calcium Fluorescence Assay for the High-Throughput Screening of Recombinant G Protein-Coupled Receptors
08:46

A "Dual-Addition" Calcium Fluorescence Assay for the High-Throughput Screening of Recombinant G Protein-Coupled Receptors

Published on: December 2, 2022

2.9K
Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
10:29

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors

Published on: May 9, 2025

2.6K

Area of Science:

  • Computational Chemistry
  • Structural Biology
  • Pharmacology

Background:

  • Structure-based drug discovery faces challenges due to the target-specific performance of scoring functions.
  • Identifying selective ligands for G protein-coupled receptors (GPCRs) remains a critical area in pharmaceutical research.

Purpose of the Study:

  • To develop and validate a consensus virtual screening method integrating energy-based scoring and molecular interaction fingerprints (IFPs).
  • To prospectively identify novel ligands for histamine H1 receptor (H1R) and beta2-adrenoceptor (ß2R) using GPCR crystal structures.
  • To demonstrate the utility of this method for predicting ligand function and guiding drug discovery efforts.

Main Methods:

  • A consensus scoring approach combining a docking scoring function with molecular interaction fingerprints (IFPs).
  • Prospective virtual screening against G protein-coupled receptor (GPCR) crystal structures, including histamine H1 receptor (H1R) and beta2-adrenoceptor (ß2R).
  • Retrospective virtual screening simulations to define scoring cut-offs and optimize receptor selection for discriminating agonists and antagonists.

Main Results:

  • Discovery of chemically novel, high-affinity histamine H1 receptor (H1R) antagonists/inverse agonists.
  • Selective structure-based identification of beta2-adrenoceptor (ß2R) agonists.
  • Experimental validation confirmed high success rates: 73% for H1R hits and 53% for ß2R hits, with nanomolar affinities and potencies.

Conclusions:

  • The consensus virtual screening method effectively identifies potent and selective GPCR ligands.
  • This approach enables structure-based prediction of GPCR ligand function, advancing drug discovery.
  • The successful identification of selective beta2-adrenoceptor agonists highlights the potential of integrating binding mode information.