The application of DOSY NMR and molecular dynamics simulations to explore the mechanism(s) of micelle binding of antimicrobial peptides containing unnatural amino acids

Tiffany D. Clark, Libero Bartolotti, Rickey Paige Hicks

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Anionic and zwitterionic micelles are often used as simple models for the lipids found in bacterial and mammalian cell membranes to investigate antimicrobial peptide-lipid interactions. In our laboratory we have employed a variety of 1D, 2D, and diffusion ordered (DOSY) NMR experiments to investigate the interactions of antimicrobial peptides containing unnatural amino acids with SDS and DPC micelles. Complete assignment of the proton spectra of these peptides is prohibited by the incorporation of a high percentage of unnatural amino acids which don't contain amide protons into the backbone. However preliminary assignment of the TOCSY spectra of compound 23 in the presence of both micelles indicated multiple conformers are present as a result of binding to these micelles. Chemical Shift Indexing agreed with previously collected CD spectra that indicated on binding to SDS micelles compound 23 adopts a mixture of α-helical structures and on binding to DPC micelles this peptide adopts a mixture of helical and β-turn/sheet like structures. DOSY NMR experiments also indicated that the total positive charge and the relative placement of that charge at the N-terminus or C-terminus are important in determining the mole fraction of the peptide that will bind to the different micelles. DOSY and 1H-NMR experiments indicated that the length of Spacer #1 plays a major role in defining the binding conformation of these analogs with SDS micelles. Results obtained from molecular simulations studies of the binding of compounds 23 and 36 with SDS micelles were consistent with the observed NMR results.

Original languageEnglish (US)
Pages (from-to)548-561
Number of pages14
JournalBiopolymers
Volume99
Issue number8
DOIs
StatePublished - Aug 1 2013

Fingerprint

Micelles
Molecular Dynamics Simulation
Peptides
Molecular dynamics
Amino acids
Nuclear magnetic resonance
Amino Acids
Computer simulation
Lipids
Protons
Experiments
Chemical shift
Cell membranes
Amides
Conformations
Cell Membrane

Keywords

  • DOSY
  • NMR spectroscopy
  • anionic and zwitterionic micelles
  • antimicrobial peptides
  • molecular dynamics simulations
  • unnatural amino acids

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Biomaterials
  • Organic Chemistry

Cite this

The application of DOSY NMR and molecular dynamics simulations to explore the mechanism(s) of micelle binding of antimicrobial peptides containing unnatural amino acids. / Clark, Tiffany D.; Bartolotti, Libero; Hicks, Rickey Paige.

In: Biopolymers, Vol. 99, No. 8, 01.08.2013, p. 548-561.

Research output: Contribution to journalArticle

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