3D structure prediction and molecular dynamics simulation studies of GPR139

Basic characteristic feature of G-protein coupled receptors (GPCRs) is that they are differentially expressed in different cells in the human body. Orphan GPCRs endogenous substrates are unknown but they are reported to be involved as major drug targets in pharmaceuticals. Probable G-protein coupled receptor 139 (GPR139), belonging to class A GPCR, is present in humans and is encoded by GPR139 gene. 3D structure prediction of GPR139 was done using threading and ab initio methods. The validation and annotation were carried out for optimized model selection. Molecular dynamics (MD) simulation of GPR139 was performed for 300ns to investigate variability of predicted model as well as seven tans membrane (7TM) domain and active site fluctuation. The active site residues were identified to investigate the potential ligand binding sites for inhibition of protein dimerization and neuropeptide receptor activity. The 3D-structure of GPR139 will be beneficial in virtual screening studies to identify potential lead compounds for therapeutic purpose.