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Modeling the Structural Communication in Supramolecular Complexes Involving GPCRs

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Membrane Protein Structure and Dynamics

Part of the book series: Methods in Molecular Biology ((MIMB,volume 914))

Abstract

This article describes a computational strategy aimed at studying the structural communication in G-Protein Coupled Receptors (GPCRs) and G proteins. The strategy relies on comparative Molecular Dynamics (MD) simulations and analyses of wild-type (i.e., reference state) vs. mutated (i.e., perturbed state), or free (i.e., reference state) vs. bound (i.e., perturbed state) forms of a GPCR or a G protein. Bound forms of a GPCR include complexes with small ligands and/or receptor dimers/oligomers, whereas bound forms of heterotrimeric GDP-bound G proteins concern the complex with a GPCR. The computational strategy includes structure prediction of a receptor monomer (in the absence of high-resolution structure), a receptor dimer/oligomer, and a receptor–G protein complex, which constitute the inputs of MD simulations. Finally, the analyses of the MD trajectories are instrumental in inferring the structural/dynamics differences between reference and perturbed states of a GPCR or a G protein. In this respect, focus will be put on the analysis of protein structure networks and communication paths.

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Acknowledgment

This study was supported by a Telethon-Italy grant n. S00068TELU and S00068TELC.

Michele Seeber, Angelo Felline, Francesco Raimondi, and Daniele Casciari deserve acknowledgment for their valuable contribution to method development.

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Authors and Affiliations

  1. Department of Chemistry, Dulbecco Telethon Institute (DTI), University of Modena and Reggio Emilia, Modena, Italy

    Francesca Fanelli

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  1. Francesca Fanelli
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Correspondence to Francesca Fanelli .

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  1. , Division of Immunology, Beckman Research Institute of the City o, E. Duarte Road 1500, Duarte, 91010, USA

    Nagarajan Vaidehi

  2. , Department of Structural Biology, University of Pittsburgh School of Medic, Fifth Avenue 3501, Pittsburgh, 15261, USA

    Judith Klein-Seetharaman

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Fanelli, F. (2012). Modeling the Structural Communication in Supramolecular Complexes Involving GPCRs. In: Vaidehi, N., Klein-Seetharaman, J. (eds) Membrane Protein Structure and Dynamics. Methods in Molecular Biology, vol 914. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-023-6_18

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  • DOI: https://doi.org/10.1007/978-1-62703-023-6_18

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-62703-022-9

  • Online ISBN: 978-1-62703-023-6

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