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

ABSTRACT

G 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
• (-)-epicatechin
• molecular docking
• molecular dynamic simulation
• adaptive biasing force

Acknowledgement

The 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 statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This 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].