Abstract
Antimicrobial peptides (AMPs) constitute an important alternative in the search for new treatments against pathogens. We analyzed the sequence variability in cytokine and chemokine proteins to investigate whether these molecules contain a sequence useful in the development of new AMPs. Cluster analysis allowed the identification of tracts, grouped in five categories showing structure and sequence homology. The structure and function relationship among these groups, was analyzed using physicochemical parameters such as length, sequence, charge, hydrophobicity and helicity, which allowed the selection of a candidate that could constitute an AMP. This peptide comprises the Cterminal alpha-helix of chemokines CXCL4/PF-457-70. Far-UV CD spectroscopy showed that this molecule adopts a random conformation in aqueous solution and the addition of 2, 2, 2 trifluoroethanol (TFE) is required to induce a helical secondary structure. The CXCL4/PF-457-70 peptide was found to have antimicrobial activity and very limited hemolytic activity. The mechanism of action was analyzed using model kinetics and molecular dynamics. The kinetic model led to a reasonable assumption about a rate constant and regulatory step on its mechanism of action. Using molecular dynamics simulations, the structural properties the CXCL4/PF-457-70 have been examined in a membrane environment. Our results show that this peptide has a strong preference for binding to the lipid head groups, consequently, increasing the surface density and decreasing the lateral mobility of the lipids alters its functionality.
Keywords: Antimicrobial peptide, cluster analysis, kinetic model, molecular simulation, Sequence Analysis, Scanning Electron Microscope
Protein & Peptide Letters
Title:Structural Analysis As an Alternative to Identify and Determine Mode of Action of Antimicrobial Peptides: Proposition of a Kinetic Model Based on Molecular Dynamics Studies
Volume: 20 Issue: 5
Author(s): Edson Edinho Robles-Gomez, Mirelle Citlali Flores-Villegas, Alicia Gonzalez-Manjarrez and Manuel Soriano-Garcia
Affiliation:
Keywords: Antimicrobial peptide, cluster analysis, kinetic model, molecular simulation, Sequence Analysis, Scanning Electron Microscope
Abstract: Antimicrobial peptides (AMPs) constitute an important alternative in the search for new treatments against pathogens. We analyzed the sequence variability in cytokine and chemokine proteins to investigate whether these molecules contain a sequence useful in the development of new AMPs. Cluster analysis allowed the identification of tracts, grouped in five categories showing structure and sequence homology. The structure and function relationship among these groups, was analyzed using physicochemical parameters such as length, sequence, charge, hydrophobicity and helicity, which allowed the selection of a candidate that could constitute an AMP. This peptide comprises the Cterminal alpha-helix of chemokines CXCL4/PF-457-70. Far-UV CD spectroscopy showed that this molecule adopts a random conformation in aqueous solution and the addition of 2, 2, 2 trifluoroethanol (TFE) is required to induce a helical secondary structure. The CXCL4/PF-457-70 peptide was found to have antimicrobial activity and very limited hemolytic activity. The mechanism of action was analyzed using model kinetics and molecular dynamics. The kinetic model led to a reasonable assumption about a rate constant and regulatory step on its mechanism of action. Using molecular dynamics simulations, the structural properties the CXCL4/PF-457-70 have been examined in a membrane environment. Our results show that this peptide has a strong preference for binding to the lipid head groups, consequently, increasing the surface density and decreasing the lateral mobility of the lipids alters its functionality.
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Edinho Robles-Gomez Edson, Citlali Flores-Villegas Mirelle, Gonzalez-Manjarrez Alicia and Soriano-Garcia Manuel, Structural Analysis As an Alternative to Identify and Determine Mode of Action of Antimicrobial Peptides: Proposition of a Kinetic Model Based on Molecular Dynamics Studies, Protein & Peptide Letters 2013; 20 (5) . https://dx.doi.org/10.2174/0929866511320050001
DOI https://dx.doi.org/10.2174/0929866511320050001 |
Print ISSN 0929-8665 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5305 |
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Therapeutic Proteins and Peptides of Plant Origin
Plants are still the major repository of biologically active substances. In the last two decades, however, natural peptides and proteins of plant origin have gained increasing attention due to their pharmacological activities over a variety of human illness, including those mediated by infections and parasitosis and those involving different cellular ...read more
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