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

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.G蛋白偶联雌激素受体（G protein estrogen receptor, GPER）已在多种生物系统中参与雌激素信号通路，并与多种病理生理过程相关联。因此，学界对筛选可结合GPER的小分子以调控其生物学活性的研究兴趣与日俱增。基于此研究目标，我们开展了以与(-)-表儿茶素（一种被报道为GPER受体配体的黄烷醇）具有化学相似性的分子为对象的GPER结合配体基于配体的虚拟筛选研究。后续通过分子对接、分子动力学模拟及自适应偏置力计算等基于结构的虚拟筛选手段，成功鉴定出对GPER具有更高结合亲和力的小分子。本研究共预测得到4种具备优异GPER结合能力的小分子，其能量相互作用均表现出良好特性。