Molecular dynamics simulation of β-adrenoceptors and their coupled G proteins

Z.-Y. Li, C.-Y. Su, B. Ding

Department of Pharmacy, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China. 1471128187@qq.com

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• Pharmacology

OBJECTIVE: G protein-coupled receptors (GPCRs) constitute the largest membrane proteins superfamily. However, the interactions between them and the coupled heterotrimeric G proteins were little known. To get a deeper view of how the receptor bound to the G protein, we carried out the molecular dynamics’ simulations of human Beta2 adrenoceptors (β1 and β2) and G protein (s and I) alpha subunit complexes by homology modeling.

MATERIALS AND METHODS: For homology modeling, the program modeller 9.11 was used with automodel module. Before dynamics simulation, the homology models were prepared by Protein Preparation Wizard module in Maestro 9.3. The Desmond program was used to perform molecular minimization and molecular dynamics simulation under OPLS-All atom 2005 force field with default parameters.

RESULTS: The results offered us the mechanism vividly in molecular level: (1) GPCR-G protein complex can be simulated without specific nanobody; (2) the G protein activation ability of GPCR can be explained by molecular dynamics simulation.

CONCLUSIONS: It is suggested that we could do molecular dynamics simulation of complex of GPCR-G protein without bound nanobody. Secondly, the simulation time reduced greatly by using homology modeling to generate complex of proteins. Thirdly, the molecular dynamics simulation will help us to know or even predict further protein-protein interactions.

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