Molecular dynamics simulations of helical antimicrobial peptides in SDS micelles: what do point mutations achieve?

Himanshu Khandelia, Yiannis N Kaznessis

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

We report long time scale simulations of the 18-residue helical antimicrobial peptide ovispirin-1 and its analogs novispirin-G10 and novispirin-T7 in SDS micelles. The SDS micelle serves as an economical and effective model for a cellular membrane. Ovispirin, which is initially placed along a micelle diameter, diffuses out to the water-SDS interface and stabilizes to an interface-bound steady state in 16.35 ns of simulation. The final conformation, orientation, and the structure of ovispirin are in good agreement with the experimentally observed properties of the peptide in presence of lipid bilayers. The simulation succeeds in capturing subtle differences of the membrane-bound peptide structure as predicted by solid state NMR. The novispirins also undergo identical diffusion patterns and similar final conformations. Although the final interface-bound states are similar, the simulations illuminate the structural and binding properties of the mutant peptides which make them less toxic compared to ovispirin. Based on previous data and the current simulations, we propose that introduction of a bend/hinge at the center of helical antimicrobial peptides (containing a specific C-terminal motif), without disrupting the helicity of the peptides might attenuate host-cell toxicity as well as improve membrane binding properties to bacterial cellular envelopes.
Udgivelsesdato: 2005-Nov
OriginalsprogEngelsk
TidsskriftPeptides
Vol/bind26
Udgave nummer11
Sider (fra-til)2037-49
Antal sider12
ISSN0196-9781
DOI
StatusUdgivet - 1. nov. 2005

Citer dette

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title = "Molecular dynamics simulations of helical antimicrobial peptides in SDS micelles: what do point mutations achieve?",
abstract = "We report long time scale simulations of the 18-residue helical antimicrobial peptide ovispirin-1 and its analogs novispirin-G10 and novispirin-T7 in SDS micelles. The SDS micelle serves as an economical and effective model for a cellular membrane. Ovispirin, which is initially placed along a micelle diameter, diffuses out to the water-SDS interface and stabilizes to an interface-bound steady state in 16.35 ns of simulation. The final conformation, orientation, and the structure of ovispirin are in good agreement with the experimentally observed properties of the peptide in presence of lipid bilayers. The simulation succeeds in capturing subtle differences of the membrane-bound peptide structure as predicted by solid state NMR. The novispirins also undergo identical diffusion patterns and similar final conformations. Although the final interface-bound states are similar, the simulations illuminate the structural and binding properties of the mutant peptides which make them less toxic compared to ovispirin. Based on previous data and the current simulations, we propose that introduction of a bend/hinge at the center of helical antimicrobial peptides (containing a specific C-terminal motif), without disrupting the helicity of the peptides might attenuate host-cell toxicity as well as improve membrane binding properties to bacterial cellular envelopes. Udgivelsesdato: 2005-Nov",
keywords = "Amino Acid Motifs, Amino Acid Substitution, Antimicrobial Cationic Peptides, Micelles, Point Mutation, Sodium Dodecyl Sulfate, Structure-Activity Relationship",
author = "Himanshu Khandelia and Kaznessis, {Yiannis N}",
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Molecular dynamics simulations of helical antimicrobial peptides in SDS micelles: what do point mutations achieve? / Khandelia, Himanshu; Kaznessis, Yiannis N.

I: Peptides, Bind 26, Nr. 11, 01.11.2005, s. 2037-49.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Molecular dynamics simulations of helical antimicrobial peptides in SDS micelles: what do point mutations achieve?

AU - Khandelia, Himanshu

AU - Kaznessis, Yiannis N

PY - 2005/11/1

Y1 - 2005/11/1

N2 - We report long time scale simulations of the 18-residue helical antimicrobial peptide ovispirin-1 and its analogs novispirin-G10 and novispirin-T7 in SDS micelles. The SDS micelle serves as an economical and effective model for a cellular membrane. Ovispirin, which is initially placed along a micelle diameter, diffuses out to the water-SDS interface and stabilizes to an interface-bound steady state in 16.35 ns of simulation. The final conformation, orientation, and the structure of ovispirin are in good agreement with the experimentally observed properties of the peptide in presence of lipid bilayers. The simulation succeeds in capturing subtle differences of the membrane-bound peptide structure as predicted by solid state NMR. The novispirins also undergo identical diffusion patterns and similar final conformations. Although the final interface-bound states are similar, the simulations illuminate the structural and binding properties of the mutant peptides which make them less toxic compared to ovispirin. Based on previous data and the current simulations, we propose that introduction of a bend/hinge at the center of helical antimicrobial peptides (containing a specific C-terminal motif), without disrupting the helicity of the peptides might attenuate host-cell toxicity as well as improve membrane binding properties to bacterial cellular envelopes. Udgivelsesdato: 2005-Nov

AB - We report long time scale simulations of the 18-residue helical antimicrobial peptide ovispirin-1 and its analogs novispirin-G10 and novispirin-T7 in SDS micelles. The SDS micelle serves as an economical and effective model for a cellular membrane. Ovispirin, which is initially placed along a micelle diameter, diffuses out to the water-SDS interface and stabilizes to an interface-bound steady state in 16.35 ns of simulation. The final conformation, orientation, and the structure of ovispirin are in good agreement with the experimentally observed properties of the peptide in presence of lipid bilayers. The simulation succeeds in capturing subtle differences of the membrane-bound peptide structure as predicted by solid state NMR. The novispirins also undergo identical diffusion patterns and similar final conformations. Although the final interface-bound states are similar, the simulations illuminate the structural and binding properties of the mutant peptides which make them less toxic compared to ovispirin. Based on previous data and the current simulations, we propose that introduction of a bend/hinge at the center of helical antimicrobial peptides (containing a specific C-terminal motif), without disrupting the helicity of the peptides might attenuate host-cell toxicity as well as improve membrane binding properties to bacterial cellular envelopes. Udgivelsesdato: 2005-Nov

KW - Amino Acid Motifs

KW - Amino Acid Substitution

KW - Antimicrobial Cationic Peptides

KW - Micelles

KW - Point Mutation

KW - Sodium Dodecyl Sulfate

KW - Structure-Activity Relationship

U2 - 10.1016/j.peptides.2005.03.058

DO - 10.1016/j.peptides.2005.03.058

M3 - Journal article

C2 - 15979758

VL - 26

SP - 2037

EP - 2049

JO - Peptides

JF - Peptides

SN - 0196-9781

IS - 11

ER -