Computational modelling reveals novel insights into GnRH receptor activation and binding dynamics.

ABSTRACT: Gonadotrophin-releasing hormone (GnRH) regulates the mammalian reproductive system by binding to its receptor (GnRH1R) and is a target for treating reproductive hormone-dependent disorders and cancers. While the inactive structure of GnRH1R is known, the active conformation and GnRH binding mode that lead to receptor activation are not fully understood. The mechanism of GnRH-induced receptor activation remains poorly understood due to the absence of experimental structures of the active GnRH1R-GnRH complex. To address this gap, we employed computational docking simulations using Rosetta, coupled with a custom Python-based elimination protocol, to identify near-native binding poses. This approach yielded two top-ranked candidates, ROS-1 and ROS-2. Molecular dynamics simulations revealed tha

SUBMITTER: Paspali E 

PROVIDER: S-EPMC12660792 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature