The Curvature Induction of Surface-Bound Antimicrobial Peptides Piscidin 1 and Piscidin 3 Varies with Lipid Chain Length

The initial steps of membrane disruption by antimicrobial peptides (AMPs) involve binding to bacterial membranes in a surface-bound (S) orientation. To evaluate the effects of lipid composition on the S state, molecular dynamics simulations of the AMPs piscidin 1 (p1) and piscidin 3 (p3) were carrie...

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Bibliographic Details
Published in:The Journal of membrane biology 2015-06, Vol.248 (3), p.455-467
Main Authors: Perrin, B. Scott, Sodt, Alexander J., Cotten, Myriam L., Pastor, Richard W.
Format: Article
Language:English
Subjects:
Antimicrobial agents
Antimicrobial Cationic Peptides - chemistry
Biochemistry
Biomedical and Life Sciences
Dimyristoylphosphatidylcholine - chemistry
Fish Proteins - chemistry
Human Physiology
Life Sciences
Lipids
Molecular biology
Molecular Dynamics Simulation
Peptides
Phosphatidylcholines - chemistry
Phosphatidylethanolamines - chemistry
Phosphatidylglycerols - chemistry
Protein Structure, Secondary
Thermodynamics
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Summary:The initial steps of membrane disruption by antimicrobial peptides (AMPs) involve binding to bacterial membranes in a surface-bound (S) orientation. To evaluate the effects of lipid composition on the S state, molecular dynamics simulations of the AMPs piscidin 1 (p1) and piscidin 3 (p3) were carried out in four different bilayers: 3:1 DMPC/DMPG, 3:1 POPC/POPG, 1:1 POPE/POPG, and 4:1 POPC/cholesterol. In all cases, the addition of 1:40 piscidin caused thinning of the bilayer, though thinning was least for DMPC/DMPG. The peptides also insert most deeply into DMPC/DMPG, spanning the region from the bilayer midplane to the headgroups, and thereby only mildly disrupting the acyl chains. In contrast, the peptides insert less deeply in the palmitoyl-oleoyl containing membranes, do not reach the midplane, and substantially disrupt the chains, i.e., the neighboring acyl chains bend under the peptide, forming a basket-like conformation. Curvature free energy derivatives calculated from the simulation pressure profiles reveal that the peptides generate positive curvature in membranes with palmitoyl and oleoyl chains but negative curvature in those with myristoyl chains. Curvature inductions predicted with a continuum elastic model follow the same trends, though the effect is weaker, and a small negative curvature induction is obtained in POPC/POPG. These results do not directly speak to the relative stability of the inserted (I) states or ease of pore formation, which requires the free energy pathway between the S and I states. Nevertheless, they do highlight the importance of lipid composition and acyl chain packing.
ISSN:0022-2631
1432-1424
DOI:10.1007/s00232-014-9733-1