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@ARTICLE{LaSala:841292,
author = {La Sala, Giuseppina and Decherchi, Sergio and De Vivo,
Marco and Rocchia, Walter},
title = {{A}llosteric {C}ommunication {N}etworks in {P}roteins
{R}evealed through {P}ocket {C}rosstalk {A}nalysis},
journal = {ACS central science},
volume = {3},
number = {9},
issn = {2374-7951},
address = {Washington, DC},
publisher = {ACS Publ.},
reportid = {FZJ-2017-08383},
pages = {949 - 960},
year = {2017},
abstract = {The detection and characterization of binding pockets and
allosteric communication in proteins is crucial for studying
biological regulation and performing drug design. Nowadays,
ever-longer molecular dynamics (MD) simulations are
routinely used to investigate the spatiotemporal evolution
of proteins. Yet, there is no computational tool that can
automatically detect all the pockets and potential
allosteric communication networks along these extended MD
simulations. Here, we use a novel and fully automated
algorithm that examines pocket formation, dynamics, and
allosteric communication embedded in microsecond-long MD
simulations of three pharmaceutically relevant proteins,
namely, PNP, A2A, and Abl kinase. This dynamic analysis uses
pocket crosstalk, defined as the temporal exchange of atoms
between adjacent pockets, along the MD trajectories as a
fingerprint of hidden allosteric communication networks.
Importantly, this study indicates that dynamic pocket
crosstalk analysis provides new mechanistic understandings
on allosteric communication networks, enriching the
available experimental data. Thus, our results suggest the
prospective use of this unprecedented dynamic analysis to
characterize transient binding pockets for structure-based
drug design},
cin = {IAS-5 / INM-9},
ddc = {540},
cid = {I:(DE-Juel1)IAS-5-20120330 / I:(DE-Juel1)INM-9-20140121},
pnm = {574 - Theory, modelling and simulation (POF3-574)},
pid = {G:(DE-HGF)POF3-574},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:28979936},
UT = {WOS:000411712800009},
doi = {10.1021/acscentsci.7b00211},
url = {https://juser.fz-juelich.de/record/841292},
}