Fmoc-RGDS based fibrils: Atomic details of their hierarchical assembly
dc.contributor.author
dc.date.accessioned
2016-01-29T12:27:10Z
dc.date.available
2016-07-28T03:00:05Z
dc.date.issued
2016
dc.identifier.issn
1463-9076
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dc.description.abstract
We describe the 3D supramolecular structure of Fmoc-RGDS fibrils, where Fmoc and RGDS refer to the hydrophobic N-(fluorenyl-9-methoxycarbonyl) group and the hydrophilic Arg-Gly-Asp-Ser peptide sequence, respectively. For this purpose, we performed atomistic all-atom molecular dynamics simulations of a wide variety of packing modes derived from both parallel and antiparallel β-sheet configurations. The proposed model, which closely resembles the cross-β core structure of amyloids, is stabilized by π-π stacking interactions between hydrophobic Fmoc groups. More specifically, in this organization, the Fmoc-groups of β-strands belonging to the same β-sheet form columns of π-stacked aromatic rings arranged in a parallel fashion. Eight of such columns pack laterally forming a compact and dense hydrophobic core, in which two central columns are surrounded by three adjacent columns on each side. In addition to such Fmoc⋯Fmoc interactions, the hierarchical assembly of the constituent β-strands involves a rich variety of intra- and inter-strand interactions. Accordingly, hydrogen bonding, salt bridges and π-π stacking interactions coexist in the highly ordered packing network proposed for the Fmoc-RGDS amphiphile. Quantum mechanical calculations, which have been performed to quantify the above referred interactions, confirm the decisive role played by the π-π stacking interactions between the rings of the Fmoc groups, even though both inter-strand and intra-strand hydrogen bonds and salt bridges also play a non-negligible role. Overall, these results provide a solid reference to complement the available experimental data, which are not precise enough to determine the fibril structure, and reconcile previous independent observations
dc.description.sponsorship
This work was supported by MICINN and FEDER funds (projects number MAT2012-34498 and CTQ2011-23156/BQU) and Generalitat de Catalunya (XRQTC, 2014SGR931, and ICREA Academia 2014 prize for M.S.)
dc.format.extent
14 p.
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application/pdf
dc.language.iso
eng
dc.publisher
Royal Society of Chemistry (RSC)
dc.relation
info:eu-repo/grantAgreement/MICINN//CTQ2011-23156/ES/AVANCES EN CATALISIS Y AROMATICIDAD/
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Versió postprint del document publicat a: http://dx-doi.org/10.1039/C5CP04269K
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© Physical Chemistry Chemical Physics, 2016, vol. 18, p. 1265-1278
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Articles publicats (D-Q)
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Tots els drets reservats
dc.source
Zanuy, David Poater i Teixidor, Jordi Solà i Puig, Miquel Hamley, Ian W. Alemán, Carlos 2016 Fmoc-RGDS based fibrils: Atomic details of their hierarchical assembly Physical Chemistry Chemical Physics 18 1265 1278
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dc.title
Fmoc-RGDS based fibrils: Atomic details of their hierarchical assembly
dc.type
info:eu-repo/semantics/article
dc.rights.accessRights
info:eu-repo/semantics/openAccess
dc.embargo.terms
12 mesos
dc.date.embargoEndDate
info:eu-repo/date/embargoEnd/2016-07-21
dc.type.version
info:eu-repo/semantics/acceptedVersion
dc.identifier.doi
dc.identifier.idgrec
024262
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dc.relation.ProjectAcronym
dc.identifier.eissn
1463-9084