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Author Notes:

Simulations were carried out by KAR, CMD and JTK, while experiments were conducted and analyzed by CMD.

KAR, CMD, RBD and JTK contributed to writing and editing the manuscript.

We would also like to acknowledge Sai Ganesan, Silvina Matysiak, Gokul Raghunath and Joel P. Schneider for helpful discussion.


Research Funding:

This material is based upon work supported by the NSF Graduate Research Fellowship Program under Grant No. DGE-1444932.

This work used the Extreme Science and Engineering Discovery Environment (XSEDE), which is supported by National Science Foundation grant number ACI-1053575, and the resources of the Cherry L. Emerson Center for Scientific Computation.

CMD analysis work at Illinois was supported by a postdoctoral fellowship provided by the Center for the Physics of Living Cells, funded by NSF PHY 1430124.

CMD experimental work at Emory was supported by the National Institutes of Health, grant GMR01 GM53640 to RBD.


  • Curvature
  • Fluorescence spectroscopy
  • Lipid bilayers
  • Liposome
  • SVS-1
  • Surface tension
  • Amino Acid Sequence
  • Antimicrobial Cationic Peptides
  • Circular Dichroism
  • Lipid Bilayers
  • Liposomes
  • Membrane Lipids
  • Membrane Proteins
  • Models, Molecular
  • Molecular Dynamics Simulation
  • Phospholipids
  • Protein Folding
  • Protein Structure, Secondary
  • Spectrometry, Fluorescence
  • Static Electricity

Binding, folding and insertion of a β-hairpin peptide at a lipid bilayer surface: Influence of electrostatics and lipid tail packing


Journal Title:

Biochimica et Biophysica Acta Molecular and Cell Biology of Lipids


Volume 1860, Number 3


, Pages 792-800

Type of Work:

Article | Post-print: After Peer Review


Antimicrobial peptides (AMPs) act as host defenses against microbial pathogens. Here we investigate the interactions of SVS-1 (KVKVKVKVDPLPTKVKVKVK), an engineered AMP and anti-cancer β-hairpin peptide, with lipid bilayers using spectroscopic studies and atomistic molecular dynamics simulations. In agreement with literature reports, simulation and experiment show preferential binding of SVS-1 peptides to anionic over neutral bilayers. Fluorescence and circular dichroism studies of a Trp-substituted SVS-1 analogue indicate, however, that it will bind to a zwitterionic DPPC bilayer under high-curvature conditions and folds into a hairpin. In bilayers formed from a 1:1 mixture of DPPC and anionic DPPG lipids, curvature and lipid fluidity are also observed to promote deeper insertion of the fluorescent peptide. Simulations using the CHARMM C36m force field offer complementary insight into timescales and mechanisms of folding and insertion. SVS-1 simulated at an anionic mixed POPC/POPG bilayer folded into a hairpin over a microsecond, the final stage in folding coinciding with the establishment of contact between the peptide's valine sidechains and the lipid tails through a “flip and dip” mechanism. Partial, transient folding and superficial bilayer contact are seen in simulation of the peptide at a zwitterionic POPC bilayer. Only when external surface tension is applied does the peptide establish lasting contact with the POPC bilayer. Our findings reveal the influence of disruption to lipid headgroup packing (via curvature or surface tension) on the pathway of binding and insertion, highlighting the collaborative effort of electrostatic and hydrophobic interactions on interaction of SVS-1 with lipid bilayers.

Copyright information:

© 2017 Elsevier B.V.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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