Ligand- and structure-based identification of GPER-binding small molecules

ABSTRACTG protein estrogen receptor (GPER) has been implicated in oestrogen-signalling routes in several biological systems and has been associated with different pathophysiological processes. So, there has been an increasing interest in identifying GPER-binding small molecules to modulate their biological activity. To this aim, we report the ligand-based virtual screening of GPER-binding molecules based on chemical similarity to (-)-epicatechin (flavanol reported as a ligand for the GPER receptor). Further structure-based screening allowed us to identify molecules with higher binding affinity to GPER based on molecular docking, molecular dynamic simulation and adaptative biasing force calculations. Here, we predicted 4 small molecules with a high ability to bind GPER exhibit favourable energy interaction.KEYWORDS: GPER(-)-epicatechinmolecular dockingmolecular dynamic simulationadaptive biasing force AcknowledgementThe authors are grateful for the computing time granted by the Supercomputer Hybrid Cluster 'Xiuhcoatl' at General Coordination of Information and Communications Technologies (CGSTIC) of Cinvestav-IPN.Disclosure statementNo potential conflict of interest was reported by the author(s).Additional informationFundingThis work was supported by Consejo Nacional de Ciencia y Tecnología [grant number 778903 Ph.D. Fellowship]; Consejo Nacional de Ciencia y Tecnología [grant number FORDECYT/PRONACES 140637]; Xiuhcoatl cluster Cinvestav [grant number 2022].