Computational study of the heterodimerization between mu and delta receptors

A growing body of evidence indicated that the G protein coupled receptors exist as homo- or hetero-dimers in the living cell. The heterodimerization between mu and delta opioid receptors has attracted researchers' particular interests, it is reported to display novel pharmacological and signalling regulation properties. In this study, we construct the full-length 3D-model of mu and delta opioid receptors using the homology modelling method. Threading program was used to predict the possible templates for the N- and C-terminus domains. Then, a 30 ns molecular dynamics simulations was performed with each receptor embedded in an explicit membrane-water environment to refine and explore the conformational space. Based on the structures extracted from the molecular dynamics, the likely interface of mu-delta heterodimer was investigated through the analysis of protein-protein docking, cluster, shape complementary and interaction energy. The computational modelling works revealed that the most likely interface of heterodimer was formed between the transmembrane1,7 (TM1,7) domains of mu receptor and the TM(4,5) domains of delta receptor, with emphasis on mu-TM1 and delta-TM4, the next likely interface was mu(TM6,7)-delta(TM4,5), with emphasis on mu-TM6 and delta-TM4. Our results were consistent with previous reports.