Rat neuromedin B receptor (rNMBR) belongs to the family A of G-protein coupled receptor (GPCR). The unique structure and important role in the signaling transduction of GPCR make them very useful for drug targets. So understanding the regulation mechanisms of rNMBR by its agonists and antagonists at the atomic level is essential for reasonably designing rNMBR antagonists as drug candidates for treating NMB-mediated diseases. A 3D model of rNMBR was constructed by homology modeling, and then molecular docking and molecular dynamics (MD) simulations were carried out. Based on the 3D structure, regulation mechanisms of rNMBR by agonists and antagonists were investigated via three 10 ns MD simulations on the systems of apo-rNMBR, rNMBR-NMB and rNMBR-pd168368. It was found that the ligand was located within the transmembrane regions 3, 5, 6, 7 (TM3, TM5, TM6, TM7) of rNMBR, NMB leading the receptor to its activated state. In contrast, binding of pd168368 to rNMBR locked rNMBR in its inactive state.

Key words: neuromedin B receptor, G-protein coupled receptor, homology modeling, molecular dynamics simulation, molecular docking