Molecular docking study for novel phosphodiesterase-IV inhibitors

Abstract

In this study, a molecular docking process for different Phosphodiesterase4 inhibitors is carried out. In the molecular modeling field, the process of docking a ligand to a binding site consists in mimicing the natural course of interaction of the ligand and its receptor via a lowest energy pathway. Before the molecular docking, X-ray crystal structures for Phosphodiesterase-IV enzyme from the Protein Databank are analysed. According to crystal structures, four pharmacophores are designed with the LigandScout software and one of them is improved with the Catalyst program. Virtual screening based on this pharmacophore model is carried out with 6 databases which contain about 2 million drug-like compounds. At the end of virtual screening, 1959 hit compounds are found. According to physicochemical filters and Lipinski rule of five, some of the compounds are marked as non-druglike compounds and they are eliminated. The docking process is performed with AutoDock 4.0 for the remaining candidate compounds. During the docking process, the binding energies, the root mean square deviation (RMSD) values and Ki (dissociation constant) are obtained for each compound. Based on these findings, some of the compounds are filtered. Finally the strain energy between the best pose of the ligands selected by AutoDock 4.0 and their optimized conformation are calculated with PM3 in Spartan.