Show simple item record

dc.contributor.authorLee, Brent L.
dc.contributor.authorKuczera, Krzysztof
dc.contributor.authorMiddaugh, C. Russell
dc.contributor.authorJas, Gouri S.
dc.date.accessioned2017-12-06T22:20:47Z
dc.date.available2017-12-06T22:20:47Z
dc.date.issued2016-06
dc.identifier.citationLee, B. L., Kuczera, K., Middaugh, C. R., & Jas, G. S. (2016). Permeation of the three aromatic dipeptides through lipid bilayers: Experimental and computational study. The Journal of chemical physics, 144(24), 245103.en_US
dc.identifier.urihttp://hdl.handle.net/1808/25599
dc.descriptionThe following article appeared in The Journal of Chemical Physics 145, 059902 (2016); doi: 10.1063/1.4954241and may be found at http://doi.org/10.1063/1.4954241.en_US
dc.description.abstractThe time-resolved parallel artificial membrane permeability assay with fluorescence detection and comprehensive computer simulations are used to study the passive permeation of three aromatic dipeptides—N-acetyl-phenylalanineamide (NAFA), N-acetyltyrosineamide (NAYA), and N-acetyl-tryptophanamide (NATA) through a 1,2-dioleoyl-sn-glycero-3-phospocholine (DOPC) lipid bilayer. Measured permeation times and permeability coefficients show fastest translocation for NAFA, slowest for NAYA, and intermediate for NATA under physiological temperature and pH. Computationally, we perform umbrella sampling simulations to model the structure, dynamics, and interactions of the peptides as a function of z, the distance from lipid bilayer. The calculated profiles of the potential of mean force show two strong effects—preferential binding of each of the three peptides to the lipid interface and large free energy barriers in the membrane center. We use several approaches to calculate the position-dependent translational diffusion coefficients D(z), including one based on numerical solution the Smoluchowski equation. Surprisingly, computed D(z) values change very little with reaction coordinate and are also quite similar for the three peptides studied. In contrast, calculated values of sidechain rotational correlation times τrot(z) show extremely large changes with peptide membrane insertion—values become 100 times larger in the headgroup region and 10 times larger at interface and in membrane center, relative to solution. The peptides’ conformational freedom becomes systematically more restricted as they enter the membrane, sampling α and β and C7eq basins in solution, α and C7eq at the interface, and C7eq only in the center. Residual waters of solvation remain around the peptides even in the membrane center. Overall, our study provides an improved microscopic understanding of passive peptide permeation through membranes, especially on the sensitivity of rotational diffusion to position relative to the bilayer.en_US
dc.publisherAIP Publishingen_US
dc.titlePermeation of the three aromatic dipeptides through lipid bilayers: Experimental and computational studyen_US
dc.typeArticleen_US
kusw.kuauthorKuczera, Krzysztof
kusw.kudepartmentChemistryen_US
dc.identifier.doi10.1063/1.4954241en_US
kusw.oaversionScholarly/refereed, publisher versionen_US
kusw.oapolicyThis item meets KU Open Access policy criteria.en_US
dc.rights.accessrightsopenAccessen_US


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record