KUKU

KU ScholarWorks

  • myKU
  • Email
  • Enroll & Pay
  • KU Directory
    • Login
    View Item 
    •   KU ScholarWorks
    • Chemistry
    • Chemistry Scholarly Works
    • View Item
    •   KU ScholarWorks
    • Chemistry
    • Chemistry Scholarly Works
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Permeation of the three aromatic dipeptides through lipid bilayers: Experimental and computational study

    Thumbnail
    View/Open
    Lee_AIP_2016.pdf (8.807Mb)
    Issue Date
    2016-06-27
    Author
    Lee, Brent L.
    Kuczera, Krzysztof
    Middaugh, C. Russell
    Jas, Gouri S.
    Publisher
    AIP Publishing
    Type
    Article
    Article Version
    Scholarly/refereed, publisher version
    Rights
    This article may be downloaded for personal use only. Any other use requires prior permission of the author and AIP Publishing. The following article appeared in Lee, 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). doi:10.1063/1.4954241 and may be found at https://doi.org/10.1063/1.4954241.
    Metadata
    Show full item record
    Abstract
    The 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-acetyltryptophanamide (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. Published by AIP Publishing. [http://dx.doi.org/10.1063/1.4954241]
    Description
    Publisher's note added August 2016: "This article was originally published online on 27 June 2016 with a sentence missing in the Acknowledgments. After the funding acknowledgments, it should read, “G.S.J. would like to thank Wilson R. Veras Tavarez and Elizabeth De Leon Olmeda of UCC for helpful comments.” AIP Publishing apologizes for this error. All online versions of the article were corrected on 28 June 2016; the article is correct as it appears in the printed version of the journal."
    URI
    http://hdl.handle.net/1808/25440
    DOI
    https://doi.org/10.1063/1.4954241
    Collections
    • Chemistry Scholarly Works [553]
    Citation
    Lee, 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). doi:10.1063/1.4954241

    Items in KU ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.


    We want to hear from you! Please share your stories about how Open Access to this item benefits YOU.


    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

    Browse

    All of KU ScholarWorksCommunities & CollectionsThis Collection

    My Account

    LoginRegister

    Statistics

    View Usage Statistics

    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

    The University of Kansas
      Contact KU ScholarWorks
    Lawrence, KS | Maps
     
    • Academics
    • Admission
    • Alumni
    • Athletics
    • Campuses
    • Giving
    • Jobs

    The University of Kansas prohibits discrimination on the basis of race, color, ethnicity, religion, sex, national origin, age, ancestry, disability, status as a veteran, sexual orientation, marital status, parental status, gender identity, gender expression and genetic information in the University’s programs and activities. The following person has been designated to handle inquiries regarding the non-discrimination policies: Director of the Office of Institutional Opportunity and Access, IOA@ku.edu, 1246 W. Campus Road, Room 153A, Lawrence, KS, 66045, (785)864-6414, 711 TTY.

     Contact KU
    Lawrence, KS | Maps