Molecular dynamics study of melatonin binding to homology modelled Mel1a G-protein coupled receptor

The Mel1a G-coupled Protein receptor (GPCR) was modelled using the I-Tasser online web service. All-atom molecular dynamics was used to improve the structure. The primary ligand melatonin was docked to the structure post molecular dynamics and structurally aligned to the X-ray crystallographic structures of the β2 adrenergic and rhodopsin GPCR’s, of the same family of proteins. A second set of all-atom molecular dynamics was undertaken with melatonin in the proposed active site which was parameterized ab initio in Gaussian16 to note any key conformational changes due to binding. The Mel1a GPCR becomes depolarized as a result of binding in the proposed active site by melatonin, based on Van der Waal interaction with amino acid residues on the extracellular side of the membrane (Ser176, Cys177, Tyr281 and Ser103).