Homology Modeling, Validation and Dynamics of the G Protein-coupled Estrogen Receptor 1 (GPER-1)

作者：Bruno Agostino; Aiello Francesca; Costantino Gabriele; Radi Marco

来源：Molecular Informatics, 2016, 35(8-9): 333-339.

DOI：10.1002/minf.201501024

• Estrogens
• GPER-1
• Molecular Dynamics Simulations
• Homology Modelling

Estrogens exert their action mainly by binding three receptors, namely estrogen receptors and (ER and ER) and GPER-1 (G-protein coupled estrogen receptor 1). While the patho-physiological role of both ER and ER has been deeply investigated, the role of GPER-1 in estrogens' signaling has not been clearly defined yet. Unfortunately, only few GPER-1 selective ligands were discovered so far, and the real efficiency of such compounds is still matter of debate. To better understand the physiological relevance of GPER-1, new selective chemical probes are higly needed. In this scenario, we report herein the generation and validation of a three-dimensional (3-D) GPER-1 homology model by means of docking studies and molecular dynamics simulations. The model thus generated was employed to (i) decipher the structural basis underlying the ability of estrogens and some Selective Estrogen Receptor Modulators (SERMs) to bind GPER-1 and classical ER and ER, and (ii) generate a reliable G1/GPER-1 complex useful in rationalizing the pharmacological profile of G1 reported in the literature. The G1/GPER-1 complex herein reported could be further exploited in drug design approaches aimed at improving the pharmacological profile of G1 or at identifying new chemical entities (NCEs) as potential modulators of GPER-1.

• 出版日期2016-9