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Insights into membrane translocation of the cell-penetrating peptide pVEC from molecular dynamics calculations

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dc.contributor.authorSARIYAR AKBULUT, BERNA
dc.contributor.authorsAlaybeyoglu, Begum; Akbulut, Berna Sariyar; Ozkirimli, Elif
dc.date.accessioned2022-03-12T20:27:55Z
dc.date.available2022-03-12T20:27:55Z
dc.date.issued2016
dc.description.abstractDiscovery of cargo carrying cell-penetrating peptides has opened a new gate in the development of peptide-based drugs that can effectively target intracellular enzymes. Success in application and development of cell-penetrating peptides in drug design depends on understanding their translocation mechanisms. In this study, our aim was to examine the bacterial translocation mechanism of the cell-penetrating pVEC peptide (LLIILRRRIRKQAHAHSK) using steered molecular dynamics (SMD) simulations. The significance of specific residues or regions for translocation was studied by performing SMD simulations on the alanine mutants and other variants of pVEC. Residue-based analysis showed that positively charged residues contribute to adsorption to the lipid bilayer and to electrostatic interactions with the lipid bilayer as peptides are translocated. Translocation takes place in three main stages; the insertion of the N-terminus into the bilayer, the inclusion of the whole peptide inside the membrane and the exit of the N-terminus from the bilayer. These three stages mirror the three regions on pVEC; namely, the hydrophobic N-terminus, the cationic midsection, and the hydrophilic C-terminus. The N-terminal truncated pVEC, I3A, L5A, R7A mutants and scramble-pVEC make weaker interactions with the lipids during translocation highlighting the contribution of the N-terminal residues and the sequence of the structural regions to the translocation mechanism. This study provides atomistic detail about the mechanism of pVEC peptide translocation and can guide future peptide-based drug design efforts.
dc.identifier.doi10.1080/07391102.2015.1117396
dc.identifier.eissn1538-0254
dc.identifier.issn0739-1102
dc.identifier.pubmed26569019
dc.identifier.urihttps://hdl.handle.net/11424/233808
dc.identifier.wosWOS:000385577300007
dc.language.isoeng
dc.publisherTAYLOR & FRANCIS INC
dc.relation.ispartofJOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectsteered molecular dynamics
dc.subjectcell-penetrating peptide
dc.subjectpVEC
dc.subjectuptake mechanism
dc.subjectLIPID-BILAYERS
dc.subjectTAT PEPTIDE
dc.subjectSIMULATIONS
dc.subjectMECHANISMS
dc.subjectINSERTION
dc.subjectKINETICS
dc.subjectDELIVERY
dc.subjectDESIGN
dc.titleInsights into membrane translocation of the cell-penetrating peptide pVEC from molecular dynamics calculations
dc.typearticle
dspace.entity.typePublication
local.avesis.id9d5e63c3-9a83-463d-8a84-51c4de3f5130
local.import.packageSS17
local.indexed.atWOS
local.indexed.atSCOPUS
local.indexed.atPUBMED
local.journal.numberofpages12
local.journal.quartileQ2
oaire.citation.endPage2398
oaire.citation.issue11
oaire.citation.startPage2387
oaire.citation.titleJOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
oaire.citation.volume34
relation.isAuthorOfPublicationa9f127d3-8332-44dd-a532-34f3ef20bdb5
relation.isAuthorOfPublication.latestForDiscoverya9f127d3-8332-44dd-a532-34f3ef20bdb5

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