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dc.creatorGrubišić, Sonja
dc.creatorBrancato, Giuseppe
dc.creatorBarone, Vincenzo
dc.date.accessioned2019-01-30T17:34:27Z
dc.date.available2019-01-30T17:34:27Z
dc.date.issued2013
dc.identifier.issn1463-9076
dc.identifier.urihttp://cer.ihtm.bg.ac.rs/handle/123456789/1192
dc.description.abstractalpha,alpha-Dialkylated amino acid residues have acquired considerable importance as effective means for introducing backbone conformation constraints in synthetic peptides. The prototype of such a class of residues, namely Aib (alpha-aminoisobutyric acid), appears to play a dominant role in determining the preferred conformations of host proteins. We have recently introduced into the standard AMBER force field some new parameters, fitted against high-level quantum mechanical (QM) data, for simulating peptides containing alpha,alpha-dialkylated residues with cyclic side chains, such as TOAC (TOAC, 2,2,6,6-tetramethylpiperidine-1-oxyl4- amino-4-carboxylic acid) and Ac(6)c (Ac(6)c = 1-aminocyclohexaneacetic acid). Here, we show that in order to accurately reproduce the observed conformational geometries and structural fluctuations of linear alpha,alpha-dialkylated peptides based on Aib, further improvements of the non-bonding and side chain torsion potential parameters have to be considered, due to the expected larger structural flexibility of linear residues with respect to cyclic ones. To this end, we present an extended set of parameters, which have been optimized by fitting the energies of multiple conformations of the Aib dipeptide analogue to corresponding QM calculations that properly account for dispersion interactions (B3LYP-D3). The quality, transferability and size-consistency of the proposed force field have been assessed both by considering a series of poly-Aib peptides, modeled at the same QM level, and by performing molecular dynamics simulations in solvents with high and low polarity. As a result, the present parameters allow one to reproduce with good reliability the available QM and experimental data, thus representing a notable improvement over current force field especially in the description of the alpha/3(10)-helix conformational equilibria of alpha,alpha-dialkylated peptides with linear and cyclic side chains.en
dc.publisherRoyal Soc Chemistry, Cambridge
dc.relationItalian Ministry for Education, University and Research (MIUR) through the FIRB Futuro in Ricerca "SUPRACARBON'' - RBFR10DAK6
dc.relationEuropean Research Council (ERC) - DREAMS: 320951
dc.relationItalian MIUR
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172035/RS//
dc.relationCOST Action "COnvergent Distributed Environment for Computational Spectroscopy (CODECS)'' - CM1002
dc.relationINFN
dc.rightsrestrictedAccess
dc.sourcePhysical Chemistry Chemical Physics
dc.titleAn improved AMBER force field for alpha,alpha-dialkylated peptides: intrinsic and solvent-induced conformational preferences of model systemsen
dc.typearticle
dc.rights.licenseARR
dcterms.abstractБароне, Винцензо; Бранцато, Гиусеппе; Грубишић, Соња;
dc.citation.volume15
dc.citation.issue40
dc.citation.spage17395
dc.citation.epage17407
dc.citation.other15(40): 17395-17407
dc.citation.rankM21
dc.identifier.pmid24022462
dc.identifier.doi10.1039/c3cp52721b
dc.identifier.rcubConv_3043
dc.identifier.scopus2-s2.0-84886935533
dc.identifier.wos000325398500045
dc.type.versionpublishedVersion


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