Role of peptide peptide interactions in aggregation: protonectins observed in equilibrium and replica exchange molecular dynamics simulations

dc.contributorUniversidade Estadual Paulista (Unesp)
dc.contributorFaculdade de Tecnologia de Catanduva
dc.creatorBaldissera, Gisele [UNESP]
dc.creatorCabrera, Marcia Perez dos Santos [UNESP]
dc.creatorChahine, Jorge [UNESP]
dc.creatorRuggiero, José Roberto [UNESP]
dc.date2015-10-21T13:14:25Z
dc.date2015-10-21T13:14:25Z
dc.date2015-04-07
dc.date.accessioned2023-09-12T06:41:54Z
dc.date.available2023-09-12T06:41:54Z
dc.identifierhttp://pubs.acs.org/doi/abs/10.1021/bi501210e
dc.identifierBiochemistry. Washington: Amer Chemical Soc, v. 54, n. 13, p. 2262-2269, 2015.
dc.identifier0006-2960
dc.identifierhttp://hdl.handle.net/11449/128848
dc.identifier10.1021/bi501210e
dc.identifierWOS:000352660000009
dc.identifier1518826294347383
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8778193
dc.descriptionProtonectin (ILGTILGLLKGL-NH2), a peptide extracted from the venom of the wasp Agelaia pallipes pallipes, promotes mast cell degranulation activity, antibiosis against Gram-positive and -negative bacteria, and chemotaxis in polymorphonucleated leukocytes. Another peptide from the same venom, Protonectin (1-6), corresponding to the first six residues of Protonectin, exhibits only chemotaxis. A 1:1 mixture of these two peptides showed positive synergistic antimicrobial effects, attributed to the formation of a heterodimer.16 The antimicrobial activity is probably related to the peptides interaction with membrane phospholipids. Equilibrium and replica exchange molecular dynamics simulations were used to investigate two systems: the interaction of Protonectins (two molecules) and that of a mixture Protonectin and Protonectin (1-6) in the environment of sodium dodecyl sulfate (SDS) micelles, which mimic bacterial membranes and are also highly anionic. We found that in both systems the peptides tend to aggregate in the aqueous environment and are held together by hydrophobic interactions and hydrogen bonds. In the equilibrium simulations, aggregated Protonectin/Protonectin (1-6) dissociates after penetrating the SDS micelle, whereas the two Protonectins remain associated throughout the simulation time. Also, in the replica exchange simulations, the Protonectins remain closer, associating through a greater number of hydrogen bonds, and were found at only one free energy minimum, whereas the peptides in the mixture display other probable distances from each other, which are significantly longer than those observed with two Protonectin molecules. Coulomb contributions and the free energy of the systems containing micelles were calculated and show that the interactions of the mixed peptides are favored, whereas the interactions between pure Protonectins are more probable. As a consequence of the preferential interaction with the micelle, the Protonectin molecule of the mixed system presents a higher helical structure content. The enhancement of the amphipathic features caused by Protonectin (1-6) can be related to the increase in the antimicrobial activity experimentally observed.
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.descriptionUniversidade Estadual Paulista, Departamento de Física, Instituto de Biociências, Letras e Ciências Exatas de São José do Rio Preto
dc.descriptionUniversidade Estadual Paulista, Departamento de Química e Ciências Ambientais, Instituto de Biociências, Letras e Ciências Exatas de São José do Rio Preto
dc.descriptionFAPESP: 2010/11823-0
dc.descriptionFAPESP: 2014/08372-7
dc.descriptionFAPESP: 2006/57122-7
dc.format2262-2269
dc.languageeng
dc.publisherAmer Chemical Soc
dc.relationBiochemistry
dc.relation2.997
dc.relation1,685
dc.rightsAcesso restrito
dc.sourceWeb of Science
dc.titleRole of peptide peptide interactions in aggregation: protonectins observed in equilibrium and replica exchange molecular dynamics simulations
dc.typeArtigo


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