Biology Reference
In-Depth Information
CHAPTER
Communication in GPCRs
3
Francesca Fanelli
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, Angelo Felline
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, and Francesco Raimondi
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Network Analysis to Uncover
the Structural
Dulbecco Telethon Institute (DTI), Rome, Italy
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Department of Chemistry, University of Modena and Reggio Emilia, Modena, Italy
CHAPTER OUTLINE
Introduction .............................................................................................................. 44
3.1 Materials........................................................................................................... 45
3.2 Methods ............................................................................................................ 45
3.2.1 Workflow of the PSN-MD and PSN-ENM Approaches.......................... 45
3.2.2 Building the PSG.............................................................................. 46
3.2.3 Search for the Shortest Communication Paths .................................... 48
3.3 Discussion......................................................................................................... 50
Summary .................................................................................................................. 56
Acknowledgments ..................................................................................................... 59
References ............................................................................................................... 59
Abstract
Protein structure network (PSN) analysis is one of the graph theory-based approaches
currently used to investigate the structural communication in biomolecular systems.
Information on system dynamics can be provided by atomistic molecular dynamics
simulations or coarse-grained Elastic Network Models paired with Normal Mode
Analysis (ENM-NMA).
This chapter describes the application of PSN analysis to uncover the structural
communication in G protein-coupled receptors (GPCRs). Strategies to highlight
changes in structural communication upon misfolding mutations, dimerization,
and activation are described.
Focus is put on the ENM-NMA-based strategy applied to the crystallographic
structures of rhodopsin in its inactive (dark) and signaling active (meta II (MII))
states, highlighting clear changes in the PSN and the centrality of the retinal chro-
mophore in differentiating the inactive and active states of the receptor.
