Search research articles

ABOUT JoVE

Overview Leadership Blog JoVE Help Center

AUTHORS

Publishing Process Editorial Board Scope & Policies Peer Review FAQ Submit

LIBRARIANS

Testimonials Subscriptions Access Resources Library Advisory Board FAQ

RESEARCH

JoVE Journal Methods Collections JoVE Encyclopedia of Experiments Archive

EDUCATION

JoVE Core JoVE Business JoVE Science Education JoVE Lab Manual Faculty Resource Center Faculty Site

Terms & Conditions of Use

Related Concept Videos

GPCRs Regulate Adenylyl Cylase Activity

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...

G Protein-coupled Receptors

G Protein-coupled Receptors

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...

GPCR Desensitization

GPCR Desensitization

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...

You might also read

Related Articles

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

Sort by

Same author

Multilayer network approaches to omics data integration in digital twins for cancer research.

Frontiers in systems biology·2026

Same author

A cannabidiol-sensitive region involved in the allosteric modulation of the α7 nicotinic receptor.

Proceedings of the National Academy of Sciences of the United States of America·2026

Same author

Changes in hepatic L-carnitine levels in people with metabolic dysfunction-associated steatotic liver disease (MASLD) assessed by magnetic resonance techniques.

Scientific reports·2026

Same author

Umbrella Sampling Workflows for Fast-Converging PMF Calculations without Artificial WHAM Constraints.

Journal of chemical theory and computation·2026

Same author

FMOPhore for hotspot identification and efficient fragment-to-lead growth strategies.

Nature communications·2026

Same author

Targeted removal of soluble Fms-like tyrosine kinase 1 in very preterm preeclampsia: a pilot trial.

Nature medicine·2026

Same journal

Targeting the ischemic cascade: Review on approved and investigational stroke therapies.

Current opinion in pharmacology·2026

Same journal

Senotherapeutic strategies for ovarian aging: Mechanistic insights and translational perspectives.

Current opinion in pharmacology·2026

Same journal

Chrono-immunotherapy in precision oncology: Circadian control of the tumor microenvironment and time-of-day optimization of immune checkpoint blockade.

Current opinion in pharmacology·2026

Same journal

Methotrexate: Integrating molecular pharmacology, systems toxicology, and precision rescue strategies.

Current opinion in pharmacology·2026

Same journal

Acupuncture and non-invasive neuromodulation-induced neuro-endocrine-immune changes associated with the amelioration of depression-like behaviors: A systematic review of animal studies.

Current opinion in pharmacology·2026

Same journal

Alopecia areata: Mechanisms, targeted therapies, and translational challenges.

Current opinion in pharmacology·2026

See all related articles

Search research articles

Related Experiment Video

Updated: Mar 17, 2026

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

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

Published on: May 9, 2025

Guiding lead optimization with GPCR structure modeling and molecular dynamics.

Alexander Heifetz¹, Tim James¹, Inaki Morao¹

¹Evotec Ltd., 114 Innovation Drive, Milton Park, Abingdon, Oxfordshire OX14 4RZ, UK.

Current Opinion in Pharmacology

|July 16, 2016

Summary

This summary is machine-generated.

Computational modeling of G-protein coupled receptors (GPCRs) aids drug discovery. Molecular dynamics simulations predict binding affinity, kinetics, and receptor flexibility, guiding the design of novel therapeutics.

More Related Videos

Optimizing the Genetic Incorporation of Chemical Probes into GPCRs for Photo-crosslinking Mapping and Bioorthogonal Chemistry in Live Mammalian Cells

Optimizing the Genetic Incorporation of Chemical Probes into GPCRs for Photo-crosslinking Mapping and Bioorthogonal Chemistry in Live Mammalian Cells

Published on: April 9, 2018

Author Spotlight: Exploring Cellular Processes by Modeling Ligands in Cryo-EM Maps

Author Spotlight: Exploring Cellular Processes by Modeling Ligands in Cryo-EM Maps

Published on: July 19, 2024

Related Experiment Videos

Last Updated: Mar 17, 2026

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

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

Published on: May 9, 2025

Optimizing the Genetic Incorporation of Chemical Probes into GPCRs for Photo-crosslinking Mapping and Bioorthogonal Chemistry in Live Mammalian Cells

Optimizing the Genetic Incorporation of Chemical Probes into GPCRs for Photo-crosslinking Mapping and Bioorthogonal Chemistry in Live Mammalian Cells

Published on: April 9, 2018

Author Spotlight: Exploring Cellular Processes by Modeling Ligands in Cryo-EM Maps

Author Spotlight: Exploring Cellular Processes by Modeling Ligands in Cryo-EM Maps

Published on: July 19, 2024

Area of Science:

Pharmacology
Computational Chemistry
Structural Biology

Background:

G-protein coupled receptors (GPCRs) are crucial drug targets.
GPCR modeling is vital for hit-to-lead and lead optimization in drug discovery.

Purpose of the Study:

To review computational approaches for GPCR modeling.
To illustrate a hierarchical GPCR modeling protocol.
To showcase prospective applications in industrial drug discovery projects.

Main Methods:

Molecular dynamics simulations.
Free energy of binding (affinity) calculations.
Analysis of ligand-induced GPCR flexibility and kinetics.
Identification of conserved water positions.
Assessment of mutation effects.

Main Results:

Computational methods can predict complex structures and key interactions.
Insights from modeling guide the design of improved drug candidates.
The hierarchical protocol is applicable to real-world drug discovery.

Conclusions:

Modern GPCR modeling protocols enhance drug discovery efficiency.
Molecular dynamics simulations offer valuable insights into receptor-ligand interactions.
This approach facilitates the design of molecules with improved pharmacological properties.