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Is It Possible to Find an Antimicrobial Peptide That Passes the Membrane Bilayer with Minimal Force Resistance? An Attempt at a Predictive Approach by Molecular Dynamics Simulation

There is still no answer to the mechanism of penetration of AMP peptides through the membrane bilayer. Several mechanisms for such a process have been proposed. It is necessary to understand whether it is possible, using the molecular dynamics method, to determine the ability of peptides of differen...

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Autores principales: Likhachev, Ilya V., Balabaev, Nikolay K., Galzitskaya, Oxana V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9180591/
https://www.ncbi.nlm.nih.gov/pubmed/35682676
http://dx.doi.org/10.3390/ijms23115997
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author Likhachev, Ilya V.
Balabaev, Nikolay K.
Galzitskaya, Oxana V.
author_facet Likhachev, Ilya V.
Balabaev, Nikolay K.
Galzitskaya, Oxana V.
author_sort Likhachev, Ilya V.
collection PubMed
description There is still no answer to the mechanism of penetration of AMP peptides through the membrane bilayer. Several mechanisms for such a process have been proposed. It is necessary to understand whether it is possible, using the molecular dynamics method, to determine the ability of peptides of different compositions and lengths to pass through a membrane bilayer. To explain the passage of a peptide through a membrane bilayer, a method for preparing a membrane phospholipid bilayer was proposed, and 656 steered molecular dynamics calculations were carried out for pulling 7 amyloidogenic peptides with antimicrobial potential, and monopeptides (homo-repeats consisting of 10 residues of the same amino acid: Poly (Ala), Poly (Leu), Poly (Met), Poly (Arg), and Poly (Glu)) with various sequences through the membrane. Among the 15 studied peptides, the peptides exhibiting the least force resistance when passing through the bilayer were found, and the maximum reaction occurred at the boundary of the membrane bilayer entry. We found that the best correlation between the maximum membrane reaction force and the calculated parameters corresponds to the instability index (the correlation coefficient is above 0.9). One of the interesting results of this study is that the 10 residue amyloidogenic peptides and their extended peptides, with nine added residue cell-penetrating peptides and four residue linkers, both with established antimicrobial activity, have the same bilayer resistance force. All calculated data are summarized and posted on the server.
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spelling pubmed-91805912022-06-10 Is It Possible to Find an Antimicrobial Peptide That Passes the Membrane Bilayer with Minimal Force Resistance? An Attempt at a Predictive Approach by Molecular Dynamics Simulation Likhachev, Ilya V. Balabaev, Nikolay K. Galzitskaya, Oxana V. Int J Mol Sci Article There is still no answer to the mechanism of penetration of AMP peptides through the membrane bilayer. Several mechanisms for such a process have been proposed. It is necessary to understand whether it is possible, using the molecular dynamics method, to determine the ability of peptides of different compositions and lengths to pass through a membrane bilayer. To explain the passage of a peptide through a membrane bilayer, a method for preparing a membrane phospholipid bilayer was proposed, and 656 steered molecular dynamics calculations were carried out for pulling 7 amyloidogenic peptides with antimicrobial potential, and monopeptides (homo-repeats consisting of 10 residues of the same amino acid: Poly (Ala), Poly (Leu), Poly (Met), Poly (Arg), and Poly (Glu)) with various sequences through the membrane. Among the 15 studied peptides, the peptides exhibiting the least force resistance when passing through the bilayer were found, and the maximum reaction occurred at the boundary of the membrane bilayer entry. We found that the best correlation between the maximum membrane reaction force and the calculated parameters corresponds to the instability index (the correlation coefficient is above 0.9). One of the interesting results of this study is that the 10 residue amyloidogenic peptides and their extended peptides, with nine added residue cell-penetrating peptides and four residue linkers, both with established antimicrobial activity, have the same bilayer resistance force. All calculated data are summarized and posted on the server. MDPI 2022-05-26 /pmc/articles/PMC9180591/ /pubmed/35682676 http://dx.doi.org/10.3390/ijms23115997 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Likhachev, Ilya V.
Balabaev, Nikolay K.
Galzitskaya, Oxana V.
Is It Possible to Find an Antimicrobial Peptide That Passes the Membrane Bilayer with Minimal Force Resistance? An Attempt at a Predictive Approach by Molecular Dynamics Simulation
title Is It Possible to Find an Antimicrobial Peptide That Passes the Membrane Bilayer with Minimal Force Resistance? An Attempt at a Predictive Approach by Molecular Dynamics Simulation
title_full Is It Possible to Find an Antimicrobial Peptide That Passes the Membrane Bilayer with Minimal Force Resistance? An Attempt at a Predictive Approach by Molecular Dynamics Simulation
title_fullStr Is It Possible to Find an Antimicrobial Peptide That Passes the Membrane Bilayer with Minimal Force Resistance? An Attempt at a Predictive Approach by Molecular Dynamics Simulation
title_full_unstemmed Is It Possible to Find an Antimicrobial Peptide That Passes the Membrane Bilayer with Minimal Force Resistance? An Attempt at a Predictive Approach by Molecular Dynamics Simulation
title_short Is It Possible to Find an Antimicrobial Peptide That Passes the Membrane Bilayer with Minimal Force Resistance? An Attempt at a Predictive Approach by Molecular Dynamics Simulation
title_sort is it possible to find an antimicrobial peptide that passes the membrane bilayer with minimal force resistance? an attempt at a predictive approach by molecular dynamics simulation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9180591/
https://www.ncbi.nlm.nih.gov/pubmed/35682676
http://dx.doi.org/10.3390/ijms23115997
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