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dc.creatorGrubišić, Sonja
dc.creatorBrancato, Giuseppe
dc.creatorPedone, Alfonso
dc.creatorBarone, Vincenzo
dc.date.accessioned2019-01-30T17:33:06Z
dc.date.available2019-01-30T17:33:06Z
dc.date.issued2012
dc.identifier.issn1463-9076
dc.identifier.urihttp://cer.ihtm.bg.ac.rs/handle/123456789/1127
dc.description.abstractThe popular biomolecular AMBER (ff99SB) force field (FF) has been extended with new parameters for the simulations of peptides containing alpha, alpha dialkylated residues with cyclic side chains. Together with the recent set of nitroxide parameters [E. Stendardo, A. Pedone, P. Cimino, M. C. Menziani, O. Crescenzi and V. Barone, Phys. Chem. Chem. Phys., 2010, 12, 11697] this extension allows treating the TOAC residue (TOAC, 2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid) widely used as a spin label in protein studies. All the conformational minima of the Ac-Ac6C-NMe (Ac = acetyl, Ac6C = 1-aminocyclohexaneacetic acid, NMe = methylamino) and Ac-TOAC-NMe dipeptides have been examined in terms of geometry and relative energy stability by Quantum Mechanical (QM) computations employing an hybrid density functional (PBE0) for an extended training set of conformers with various folds. A very good agreement between QM and MM (molecular mechanics) data has been obtained in most of the investigated properties, including solvent effects. Finally, the new set of parameters has been validated by comparing the conformational and dynamical behavior of TOAC-labeled polypeptides investigated by means of classical molecular dynamics (MD) simulations with QM data and experimental evidence. The new FF accurately describes the tuning of conformational and dynamical behavior of the Ac-TOAC-NMe dipeptide and double spin-labeled heptapeptide Fmoc-(Aib-Aib-TOAC)(2)-Aib-OMe (Fmoc, fluorenyl-9-methoxycarbonyl; Aib, alpha-aminoisobutyric acid; OMe, methoxy) by solvents with different polarity. In particular, we found that the 3(10) helical structure of heptapeptide is the most stable one in vacuo, with a geometry very similar to the X-ray crystallographic structure, whereas a conformational equilibrium between the 3(10)- and alpha-helical structures is established in aqueous solution, in agreement with EPR data.en
dc.publisherRoyal Soc Chemistry, Cambridge
dc.relationItalian Ministry for Education, University and Research (MIUR)
dc.relationINFN
dc.relationCOST Action "COnvergent Distributed Environment for Computational Spectroscopy (CODECS)'' - CM1002
dc.rightsrestrictedAccess
dc.sourcePhysical Chemistry Chemical Physics
dc.titleExtension of the AMBER force field to cyclic alpha,alpha dialkylated peptidesen
dc.typearticle
dc.rights.licenseARR
dcterms.abstractГрубишић, Соња; Бранцато, Гиусеппе; Бароне, Винцензо; Педоне, Aлфонсо;
dc.citation.volume14
dc.citation.issue44
dc.citation.spage15308
dc.citation.epage15320
dc.citation.other14(44): 15308-15320
dc.citation.rankM21
dc.identifier.pmid23051698
dc.identifier.doi10.1039/c2cp42713c
dc.identifier.rcubConv_2871
dc.identifier.scopus2-s2.0-84867928399
dc.identifier.wos000310153300008
dc.type.versionpublishedVersion


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