Modeling of the hEP1 receptor based on the crystallographic structure of beta(2)-adrenergic receptor and its assessment with docking studies and molecular dynamics simulation

Abstract

Introduction: The human EP1 (hEP1) prostanoid receptor is a G-Protein Coupled Receptor (GPCR)which plays important physiological roles in some systems in the body like cardiovascular and immune systems and could be a very important target for drug design. Materials and methods: To understand the molecular structure of hEP1 receptor, a homology model of the receptor was constructed from the 2.4 angstrom resolution crystal structure of human beta(2)-adrenergic receptor (PDB code: 2RH1), using three different sequence alignments. The model including PGE(2) inside the active site was Subjected to molecular dynamics simulation. Docking studies were performed for PGE(2) and 10 prostanoid analogs in the active site of the modeled receptor. Results and Discussion: The structure of modeled receptor remained stable during the 10 nanosecond(ns) simulation. In the docking simulations a correlation of r(2)=0.74 was observed between the K. values and the docking scores of the prostanoid Compounds. The structure which was modeled in the present study can be used in the structure-based drug design, helping the rational design of novel ligands for the hEP1 receptor.