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Multiscale models of the antimicrobial peptide protegrin-1 on gram-negative bacteria membranes.

Bolintineanu DS, Vivcharuk V, Kaznessis YN - Int J Mol Sci (2012)

Bottom Line: We present a summary of computational investigations in our lab aimed at understanding this unique mechanism of action, in particular the development of models that provide a quantitative connection between molecular-level biophysical phenomena and relevant biological effects.Using fully atomistic molecular dynamics simulations, we have computed the thermodynamics of peptide-membrane association and insertion, as well as peptide aggregation.Overall, this work provides a quantitative mechanistic description of the mechanism of action of protegrin antimicrobial peptides across multiple length and time scales.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemical Engineering and Materials Science, University of Minnesota, 421 Washington Ave SE, Minneapolis, MN 55455, USA; E-Mails: dan.bolintineanu@gmail.com (D.S.B.); vivch001@gmail.com (V.V.).

ABSTRACT
Antimicrobial peptides (AMPs) are naturally-occurring molecules that exhibit strong antibiotic properties against numerous infectious bacterial strains. Because of their unique mechanism of action, they have been touted as a potential source for novel antibiotic drugs. We present a summary of computational investigations in our lab aimed at understanding this unique mechanism of action, in particular the development of models that provide a quantitative connection between molecular-level biophysical phenomena and relevant biological effects. Our work is focused on protegrins, a potent class of AMPs that attack bacteria by associating with the bacterial membrane and forming transmembrane pores that facilitate the unrestricted transport of ions. Using fully atomistic molecular dynamics simulations, we have computed the thermodynamics of peptide-membrane association and insertion, as well as peptide aggregation. We also present a multi-scale analysis of the ion transport properties of protegrin pores, ranging from atomistic molecular dynamics simulations to mesoscale continuum models of single-pore electrodiffusion to models of transient ion transport from bacterial cells. Overall, this work provides a quantitative mechanistic description of the mechanism of action of protegrin antimicrobial peptides across multiple length and time scales.

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Current-voltage relationship of a protegrin pore.
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f6-ijms-13-11000: Current-voltage relationship of a protegrin pore.

Mentions: where ci, Di and qi are the concentration, diffusivity and valence of each ionic species, ϕ is the electrostatic potential, e, kB and T are the elementary charge, Boltzmann’s constant and temperature, respectively, ɛ is the space-dependent dielectric constant, and ρf is the fixed charge density. The electrostatic potential is obtained by solving the Poisson equation (9) consistently with (8), and the net current is determined based on the resulting ion fluxes. The computed current-voltage (I-V) relationship is shown in Figure 6 below, along with experimental data from [6].


Multiscale models of the antimicrobial peptide protegrin-1 on gram-negative bacteria membranes.

Bolintineanu DS, Vivcharuk V, Kaznessis YN - Int J Mol Sci (2012)

Current-voltage relationship of a protegrin pore.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3472726&req=5

f6-ijms-13-11000: Current-voltage relationship of a protegrin pore.
Mentions: where ci, Di and qi are the concentration, diffusivity and valence of each ionic species, ϕ is the electrostatic potential, e, kB and T are the elementary charge, Boltzmann’s constant and temperature, respectively, ɛ is the space-dependent dielectric constant, and ρf is the fixed charge density. The electrostatic potential is obtained by solving the Poisson equation (9) consistently with (8), and the net current is determined based on the resulting ion fluxes. The computed current-voltage (I-V) relationship is shown in Figure 6 below, along with experimental data from [6].

Bottom Line: We present a summary of computational investigations in our lab aimed at understanding this unique mechanism of action, in particular the development of models that provide a quantitative connection between molecular-level biophysical phenomena and relevant biological effects.Using fully atomistic molecular dynamics simulations, we have computed the thermodynamics of peptide-membrane association and insertion, as well as peptide aggregation.Overall, this work provides a quantitative mechanistic description of the mechanism of action of protegrin antimicrobial peptides across multiple length and time scales.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemical Engineering and Materials Science, University of Minnesota, 421 Washington Ave SE, Minneapolis, MN 55455, USA; E-Mails: dan.bolintineanu@gmail.com (D.S.B.); vivch001@gmail.com (V.V.).

ABSTRACT
Antimicrobial peptides (AMPs) are naturally-occurring molecules that exhibit strong antibiotic properties against numerous infectious bacterial strains. Because of their unique mechanism of action, they have been touted as a potential source for novel antibiotic drugs. We present a summary of computational investigations in our lab aimed at understanding this unique mechanism of action, in particular the development of models that provide a quantitative connection between molecular-level biophysical phenomena and relevant biological effects. Our work is focused on protegrins, a potent class of AMPs that attack bacteria by associating with the bacterial membrane and forming transmembrane pores that facilitate the unrestricted transport of ions. Using fully atomistic molecular dynamics simulations, we have computed the thermodynamics of peptide-membrane association and insertion, as well as peptide aggregation. We also present a multi-scale analysis of the ion transport properties of protegrin pores, ranging from atomistic molecular dynamics simulations to mesoscale continuum models of single-pore electrodiffusion to models of transient ion transport from bacterial cells. Overall, this work provides a quantitative mechanistic description of the mechanism of action of protegrin antimicrobial peptides across multiple length and time scales.

Show MeSH
Related in: MedlinePlus