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@ARTICLE{Ponzoni:827445,
author = {Ponzoni, Luca and Rossetti, Giulia and Maggi, Luca and
Giorgetti, Alejandro and Carloni, Paolo and Micheletti,
Cristian},
title = {{U}nifying view of mechanical and functional hotspots
across class {A} {GPCR}s},
journal = {PLoS Computational Biology},
volume = {13},
number = {2},
issn = {1553-7358},
address = {San Francisco, Calif.},
publisher = {Public Library of Science},
reportid = {FZJ-2017-01570},
pages = {e1005381 -},
year = {2017},
abstract = {G protein-coupled receptors (GPCRs) are the largest
superfamily of signaling proteins. Their activation process
is accompanied by conformational changes that have not yet
been fully uncovered. Here, we carry out a novel comparative
analysis of internal structural fluctuations across a
variety of receptors from class A GPCRs, which currently has
the richest structural coverage. We infer the local
mechanical couplings underpinning the receptors’
functional dynamics and finally identify those amino acids
whose virtual deletion causes a significant softening of the
mechanical network. The relevance of these amino acids is
demonstrated by their overlap with those known to be crucial
for GPCR function, based on static structural criteria. The
differences with the latter set allow us to identify those
sites whose functional role is more clearly detected by
considering dynamical and mechanical properties. Of these
sites with a genuine mechanical/dynamical character, the top
ranking is amino acid 7x52, a previously unexplored, and
experimentally verifiable key site for GPCR conformational
response to ligand binding.},
cin = {IAS-5 / INM-11 / INM-9 / JSC / JARA-HPC},
ddc = {570},
cid = {I:(DE-Juel1)IAS-5-20120330 / I:(DE-Juel1)INM-11-20170113 /
I:(DE-Juel1)INM-9-20140121 / I:(DE-Juel1)JSC-20090406 /
$I:(DE-82)080012_20140620$},
pnm = {574 - Theory, modelling and simulation (POF3-574) / 511 -
Computational Science and Mathematical Methods (POF3-511) /
Towards the design of allosteric ligands binding to the
human muscarinic receptor M2 $(jias59_20161101)$},
pid = {G:(DE-HGF)POF3-574 / G:(DE-HGF)POF3-511 /
$G:(DE-Juel1)jias59_20161101$},
typ = {PUB:(DE-HGF)16},
UT = {WOS:000395718800027},
pubmed = {pmid:28158180},
doi = {10.1371/journal.pcbi.1005381},
url = {https://juser.fz-juelich.de/record/827445},
}