Related Experiment Video
Updated: Aug 6, 2026
10:59
Visualizing the Conformational Dynamics of Membrane Receptors Using Single-Molecule FRET
Published on: August 17, 2022
Mapping the relationship between receptor dynamics and function in G protein-coupled receptors using molecular
Adrián García-Recio1, Alejandro Peralta-García1, Anna Korda1
1Research Programme on Biomedical Informatics (GRIB), Hospital del Mar Medical Research Institute (IMIM) & Department of Medicine and Life Sciences at Universitat Pompeu Fabra, Barcelona, Spain.
Current Opinion in Structural Biology
|July 22, 2026
Summary
Molecular dynamics simulations reveal the dynamic conformational landscape of G protein-coupled receptors (GPCRs), offering insights beyond static structures. These simulations uncover transient states and interactions crucial for drug discovery and understanding receptor function.
Area of Science:
- Biochemistry
- Structural Biology
- Computational Biology
Background:
- G protein-coupled receptors (GPCRs) are crucial cellular signaling regulators and significant drug targets.
- Static structural methods like X-ray crystallography and cryo-EM capture limited receptor conformations.
- Understanding GPCR dynamics is essential for comprehending their function and for drug development.
Purpose of the Study:
- To explore the conformational landscape of GPCRs using molecular dynamics (MD) simulations.
- To complement static structural data with dynamic insights into GPCR behavior.
- To investigate how receptor dynamics influence ligand recognition and signaling bias.
Main Methods:
- Utilized large-scale molecular dynamics (MD) simulations.
- Employed resources like GPCRmd for systematic exploration of GPCR motions.
- Analyzed simulation data to identify transient conformational states and interactions.
Main Results:
- MD simulations revealed diverse, transient conformational states of GPCRs.
- Identified cryptic binding pockets and the role of lipids and water in receptor function.
- Uncovered allosteric communication networks influencing ligand binding and signaling.
Conclusions:
- MD simulations provide a dynamic view of GPCRs, complementing static structures.
- These dynamic insights are critical for understanding GPCR function, ligand interactions, and signaling bias.
- Computational approaches like MD simulations are invaluable for GPCR research and drug discovery.
Related Concept Videos
01:15G 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...
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...
01:15G 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...
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...
01:21G-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.
01:21G-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.
01:30Transducer 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...
GPCRs are also called heptahelical, 7TM, or...
01:22Activation and Inactivation of G Proteins
Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high affinity and are together...