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Updated: Jan 10, 2026
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Visualizing the Conformational Dynamics of Membrane Receptors Using Single-Molecule FRET
Published on: August 17, 2022
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Computational modelling reveals novel insights into GnRH receptor activation and binding dynamics
Elpiniki Paspali1, Valerie Anne Ferro2, Karina Kubiak-Ossowska3
1Chemical & Process Engineering, University of Strathclyde, G1 1XL, Glasgow, UK.
Scientific Reports
|November 27, 2025
Summary
This study reveals the active structure of the Gonadotrophin-releasing hormone receptor (GnRH1R) bound to GnRH, detailing key interactions and communication pathways. This advances understanding of reproductive system regulation and potential therapeutic targets.
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- Gonadotrophin-releasing hormone (GnRH) is crucial for mammalian reproduction and a therapeutic target for hormone-dependent disorders.
- The active conformation and GnRH binding mechanism of the GnRH receptor (GnRH1R) remain poorly understood due to a lack of experimental structures.
Purpose of the Study:
- To elucidate the active conformation and binding mode of the GnRH-GnRH1R complex using computational methods.
- To identify key molecular interactions and signaling pathways involved in GnRH-induced receptor activation.
Main Methods:
- Computational docking simulations using Rosetta to predict binding poses.
- Custom Python-based elimination protocol to refine candidate poses.
- Molecular dynamics simulations to analyze receptor activation and dynamics.
Main Results:
- Identified two top binding poses, ROS-1 and ROS-2, with ROS-1 inducing receptor activation within 1.0 μs.
- Characterized key interactions including π-π stacking and hydrogen bonds between GnRH and GnRH1R.
- Revealed two major communication pathways initiated by GnRH residue R8, involving specific motifs and lipid interactions.
Conclusions:
- Provided a detailed model of the active GnRH-GnRH1R complex, clarifying binding dynamics and activation mechanisms.
- Consolidated previous findings and offered a coherent picture of receptor activation.
- Paved the way for improved therapeutic strategies targeting reproductive disorders.
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