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dc.contributor.author
Formoso, Elena
dc.contributor.author
Limongelli, Vittorio
dc.contributor.author
Parrinello, Michele
dc.date.accessioned
2017-11-13T12:53:59Z
dc.date.available
2017-06-14T03:24:43Z
dc.date.available
2017-07-04T15:06:25Z
dc.date.available
2017-06-11T22:02:16Z
dc.date.available
2017-11-13T12:53:59Z
dc.date.issued
2015-02-12
dc.identifier.other
10.1038/srep08425
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/207390
dc.identifier.doi
10.3929/ethz-a-010573174
dc.description.abstract
Adenylate Kinase (AK) is a signal transducing protein that regulates cellular energy homeostasis balancing between different conformations. An alteration of its activity can lead to severe pathologies such as heart failure, cancer and neurodegenerative diseases. A comprehensive elucidation of the large-scale conformational motions that rule the functional mechanism of this enzyme is of great value to guide rationally the development of new medications. Here using a metadynamics-based computational protocol we elucidate the thermodynamics and structural properties underlying the AK functional transitions. The free energy estimation of the conformational motions of the enzyme allows characterizing the sequence of events that regulate its action. We reveal the atomistic details of the most relevant enzyme states, identifying residues such as Arg119 and Lys13, which play a key role during the conformational transitions and represent druggable spots to design enzyme inhibitors. Our study offers tools that open new areas of investigation on large-scale motion in proteins.
en_US
dc.language.iso
en
en_US
dc.publisher
Nature Publishing Group
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
Computational biophysics
en_US
dc.subject
Computational chemistry
en_US
dc.subject
Molecular dynamics
en_US
dc.title
Energetics and Structural Characterization of the large-scale Functional Motion of Adenylate Kinase
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
dc.date.published
2015-02-12
ethz.journal.title
Scientific Reports
ethz.journal.volume
5
en_US
ethz.pages.start
8425
en_US
ethz.size
8 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.code.ddc
5 - Science::540 - Chemistry
en_US
ethz.code.ddc
5 - Science::570 - Life sciences
en_US
ethz.publication.place
London
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02020 - Dep. Chemie und Angewandte Biowiss. / Dep. of Chemistry and Applied Biosc.::02515 - Laboratorium für Physikalische Chemie / Laboratory of Physical Chemistry
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02020 - Dep. Chemie und Angewandte Biowiss. / Dep. of Chemistry and Applied Biosc.::03575 - Parrinello, Michele / Parrinello, Michele
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02020 - Dep. Chemie und Angewandte Biowiss. / Dep. of Chemistry and Applied Biosc.::03575 - Parrinello, Michele / Parrinello, Michele
ethz.date.deposited
2017-06-11T22:02:43Z
ethz.source
ECOL
ethz.source
ECIT
ethz.identifier.importid
imp59366b835328541798
ethz.identifier.importid
imp593653d173d0117070
ethz.ecolpid
eth:48410
ethz.ecitpid
pub:169566
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2017-11-13T12:49:16Z
ethz.rosetta.lastUpdated
2019-01-02T10:43:47Z
ethz.rosetta.exportRequired
true
ethz.rosetta.versionExported
true
dc.identifier.olduri
http://hdl.handle.net/20.500.11850/108577
dc.identifier.olduri
http://hdl.handle.net/20.500.11850/155353
ethz.COinS
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