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Related Concept Videos

G Protein-coupled Receptors01:15

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...
G Protein-coupled Receptors01:15

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...
G-protein Coupled Receptors01:21

G-protein Coupled Receptors

G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.
G-protein Coupled Receptors01:21

G-protein Coupled Receptors

G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.
Transducer Mechanism: G Protein–Coupled Receptors01:30

Transducer Mechanism: G Protein–Coupled Receptors

G Protein–Coupled Receptors (GPCRs) are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to various stimuli. GPCRs regulate critical physiological pathways and are excellent drug targets for treating diseases such as diabetes, cancer, obesity, depression, or Alzheimer's. Nearly 35% of approved drugs implement their therapeutic effects by selectively interacting with specific GPCRs.
GPCRs are also called heptahelical, 7TM, or...
The Two-State Receptor Model01:29

The Two-State Receptor Model

The two-state receptor model explains a drug's interaction with receptors, such as G protein-coupled receptors and ligand-gated ion channels, to induce or inhibit a biological response. When no natural ligands are present, a receptor exists in an equilibrium of inactive (Ri) and active (Ra) conformations. The inactive form does not produce a response, while the active form generates a basal effect known as constitutive activity.
The binding affinity of a drug determines its interaction with one...

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Related Experiment Video

Updated: Jun 17, 2026

Strategic Screening and Characterization of the Visual GPCR-mini-G Protein Signaling Complex for Successful Crystallization
09:19

Strategic Screening and Characterization of the Visual GPCR-mini-G Protein Signaling Complex for Successful Crystallization

Published on: March 16, 2020

Customizing G Protein-coupled receptor models for structure-based virtual screening.

Chris de Graaf1, Didier Rognan

  • 1Structural Chemogenomics group, Laboratory of Therapeutic Innovation, UMR7200 CNRS-UdS (Université de Strasbourg), F-67400 Illkirch, France. C.de.Graaf@few.vu.nl

Current Pharmaceutical Design
|December 24, 2009
PubMed
Summary
This summary is machine-generated.

This review details building and validating G protein-coupled receptor models for structure-based virtual screening. Despite potential inaccuracies, these models effectively identify novel drug ligands.

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Last Updated: Jun 17, 2026

Strategic Screening and Characterization of the Visual GPCR-mini-G Protein Signaling Complex for Successful Crystallization
09:19

Strategic Screening and Characterization of the Visual GPCR-mini-G Protein Signaling Complex for Successful Crystallization

Published on: March 16, 2020

Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis
08:49

Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis

Published on: June 20, 2025

Area of Science:

  • Biochemistry
  • Structural Biology
  • Computational Chemistry

Background:

  • G protein-coupled receptors (GPCRs) are crucial drug targets, necessitating accurate structural models for drug discovery.
  • Homology modeling and analysis of crystal structures are key to understanding GPCRs and developing screening strategies.

Purpose of the Study:

  • To provide practical guidance on constructing, refining, and validating GPCR models for structure-based virtual screening.
  • To present strategies for overcoming common challenges in GPCR receptor modeling workflows.
  • To analyze the utility of GPCR models in identifying novel ligands through virtual screening.

Main Methods:

  • Comparative analysis of current GPCR crystal structures and their impact on homology modeling.
  • Detailed discussion of receptor modeling workflow steps, including experimental anchors, sequence alignment, and binding cavity adjustments.
  • Application of receptor-ligand interaction fingerprint scoring for binding mode prediction and virtual screening.

Main Results:

  • Demonstration of practical tips and tricks for GPCR modeling and virtual screening exercises.
  • Inclusion of examples across major GPCR classes: rhodopsin-like (Class A), secretin-like (Class B), and glutamate-like (Class C).
  • Validation of GPCR models, even with structural inaccuracies, for efficient structure-based virtual screening.

Conclusions:

  • GPCR models are valuable tools for structure-based virtual screening, enabling the discovery of novel ligands.
  • Addressing specific modeling challenges, such as proline-induced kinks and extracellular loop modeling, enhances model reliability.
  • The presented workflow and analysis offer a robust framework for GPCR-focused drug discovery efforts.