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Computational study of the heterodimerization between μ and δ receptors

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Abstract

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 μ and δ 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 μ and δ 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 μ–δ 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 μ receptor and the TM(4,5) domains of δ receptor, with emphasis on μ-TM1 and δ-TM4, the next likely interface was μ(TM6,7)-δ(TM4,5), with emphasis on μ-TM6 and δ-TM4. Our results were consistent with previous reports.

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (Nos. 20772052, 20621091, and 20525206), the Specialized Research Fund for the Doctoral Program in Higher Education Institutions (No. 20060730017), and the Chang Jiang Program of the Ministry of Education of China. The authors thank The High Performance Center of Lanzhou University for providing computational resource.

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  1. Institute of Biochemistry and Molecular Biology, School of Basic Medical Science, State Key Laboratory of Applied Organic Chemistry, Lanzhou University, 222 Tianshui South Road, 730000, Lanzhou, China

    Xin Liu, Ming Kai, Lian Jin & Rui Wang

  2. State Key Laboratory of Chinese Medicine and Molecular Pharmacology, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Kowloon, Hong Kong, China

    Rui Wang

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  1. Xin Liu
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Liu, X., Kai, M., Jin, L. et al. Computational study of the heterodimerization between μ and δ receptors. J Comput Aided Mol Des 23, 321–332 (2009). https://doi.org/10.1007/s10822-009-9262-7

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