Design and Evaluation of New Potent G-Protein Coupled Receptor Kinase Inhibitors Using Virtual Screening Methods

Document Type : Research Article


1 Department of Chemistry, Payame Noor University, P. O. BOX 19395-3697, Tehran, Iran

2 Department of Chemistry, Payame Noor University. P. O. BOX 19395-3697, Tehran, Iran


The G-protein receptor kinases are members of the most effective enzymes in the incidence of some important disease such as cardiovascular diseases, hypertension and Alzheimer’s disease. One of these enzymes is a protein with PDB code: 3v5w in the protein data bank. The in-silico study on the interaction of variety of inhibitor ligands with this enzyme was performed. The results of the interaction between selected ligands and target protein were investigated and analyzed using molecular screening by molecular docking simulation methods. The calculations of some factors such as binding energy between ligands and target protein, non-bonding interactions of ligands in the active site of enzyme and analysis of the result of molecular docking scoring were performed. The results were compared with a standard inhibitor (Paroxetine). Furthermore, to better evaluate and correct the selection of the lead compound, the related properties of absorption, distribution, metabolism, excretion and toxicity (ADMET) of high-scored ligands were compared with pharmacokinetic factors of Paroxetine using ADMETLab 2.0 data server platform. As the result, the compound L10, (4R,5S)-5-(1,3-benzodioxol-5-yloxymethyl)-4-(4-fluorophenyl)piperidin-2-one was introduced as a novel potent inhibitor ligand which has the better potency, more binding energy and more appropriate pharmacokinetic properties.


Main Subjects