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dc.contributor.author
Musiani, Francesco
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Rossetti, Giulia
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Capece, Luciana
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Gerger, Thomas Martin
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Micheletti, Cristian
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Varani, Gabriele
dc.contributor.author
Carloni, Paolo
dc.date.available
2018-01-12T18:38:13Z
dc.date.issued
2014-10
dc.identifier.citation
Carloni, Paolo; Varani, Gabriele; Musiani, Francesco; Micheletti, Cristian; Rossetti, Giulia; Gerger, Thomas Martin; et al.; Molecular Dynamics Simulations Identify Time Scale of Conformational Changes Responsible for Conformational Selection in Molecular Recognition of HIV-1 Transactivation Responsive RNA; American Chemical Society; Journal of the American Chemical Society; 136; 44; 10-2014; 15631-15637
dc.identifier.issn
0002-7863
dc.identifier.uri
http://hdl.handle.net/11336/33089
dc.description.abstract
The HIV-1 Tat protein and several small molecules bind to HIV-1 transactivation responsive RNA (TAR) by selecting sparsely populated but pre-existing conformations. Thus, a complete characterization of TAR conformational ensemble and dynamics is crucial to understand this paradigmatic system and could facilitate the discovery of new antivirals targeting this essential regulatory element. We show here that molecular dynamics simulations can be effectively used toward this goal by bridging the gap between functionally relevant time scales that are inaccessible to current experimental techniques. Specifically, we have performed several independent microsecond long molecular simulations of TAR based on one of the most advanced force fields available for RNA, the parmbsc0 AMBER. Our simulations are first validated against available experimental data, yielding an excellent agreement with measured residual dipolar couplings and order parameter S2. This contrast with previous molecular dynamics simulations (Salmon et al., J. Am. Chem. Soc. 2013 135, 5457–5466) based on the CHARMM36 force field, which could achieve only modest accord with the experimental RDC values. Next, we direct the computation toward characterizing the internal dynamics of TAR over the microsecond time scale. We show that the conformational fluctuations observed over this previously elusive time scale have a strong functionally oriented character in that they are primed to sustain and assist ligand binding.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
American Chemical Society
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Molecular Dynamics
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Hiv
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Tar
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Rna
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Otras Ciencias Químicas
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Ciencias Químicas
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CIENCIAS NATURALES Y EXACTAS
dc.title
Molecular Dynamics Simulations Identify Time Scale of Conformational Changes Responsible for Conformational Selection in Molecular Recognition of HIV-1 Transactivation Responsive RNA
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-01-11T19:35:44Z
dc.journal.volume
136
dc.journal.number
44
dc.journal.pagination
15631-15637
dc.journal.pais
Estados Unidos
dc.description.fil
Fil: Musiani, Francesco. Scuola Internazionale Superiore di Studi Avanzati; Italia. Università di Bologna; Italia. Helmholtz Gemeinschaft. Forschungszentrum Jülich; Alemania
dc.description.fil
Fil: Rossetti, Giulia. Helmholtz Gemeinschaft. Forschungszentrum Jülich; Alemania
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Fil: Capece, Luciana. International Centre for Genetic Engineering and Biotechnology; Italia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Gerger, Thomas Martin. Helmholtz Gemeinschaft. Forschungszentrum Jülich; Alemania
dc.description.fil
Fil: Micheletti, Cristian. Scuola Internazionale Superiore di Studi Avanzati; Italia
dc.description.fil
Fil: Varani, Gabriele. University of Washington; Estados Unidos
dc.description.fil
Fil: Carloni, Paolo. Helmholtz Gemeinschaft. Forschungszentrum Jülich; Alemania
dc.journal.title
Journal of the American Chemical Society
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1021/ja507812v
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://pubs.acs.org/doi/10.1021/ja507812v
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