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

Abstract

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.