Molecular Docking Study on the Interaction of Rhodopsin-like Receptors with Tetracoordinated Gold(III) Complexes

Abstract

The pharmacologic properties of gold compounds have been known since the end of the 19th century. In the last decade gold complexes have received increased attention due to the variety of their applications. Rhodopsin-like receptors are a family of proteins that belong to the largest group of G-protein-coupled receptors (GPCRs). In this paper the molecular interactions between the active binding sites of rhodopsin-like receptors (RLRs) and synthesized gold(III) complexes ([Au(DPP)Cl2]+, where DPP = 4,7-diphenyl-1,10-phenanthroline) were investigated through molecular docking simulations. The crystal structure of investigated RLRs (PDB ID: 4A4M) was extracted from the RCSB Protein Data Bank in a PDB format. The native bound ligand (11-cis-retinal) was extracted from receptors and a binding pocket analysis was performed. Redocking was performed with gold(III) complexes to generate the same docking pose as found in the cocrystallized form of receptors. The binding energy of gold(III) complexes to RLRs was found to be −35.35 kJ/mol, as opposed to 11-cis-retinal, where it was about −40.5 kJ/mol. The obtained results revealed that gold(III) complexes bind at the same binding pockets to RLRs, as well as native bound ligands, via weak noncovalent interactions. The most prominent interactions are hydrogen bonds, alkyl–π and π–π interactions. The preliminary results suggest that gold(III) complexes showed good binding affinity against RLRs as well as the native bound ligand 11-cis-retinal, as evident from the free binding energy (ΔGbind in kJ/mol).