Limits...
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.

Show MeSH

Related in: MedlinePlus

PMFs of adsorption for protegrin monomers and dimers on 1:3 POPE:POPG lipid bilayers. D is the separation distance between the PG-1 center of mass and the phosphate plane of the upper leaflet of the membrane. From [12] with permission.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f2-ijms-13-11000: PMFs of adsorption for protegrin monomers and dimers on 1:3 POPE:POPG lipid bilayers. D is the separation distance between the PG-1 center of mass and the phosphate plane of the upper leaflet of the membrane. From [12] with permission.

Mentions: The study of protein-membrane systems by experimental techniques is cumbersome due to the extremely fast time scales and small length scales of the relevant physical phenomena. To address these shortcomings, we have carried out molecular dynamics (MD) simulations coupled to free energy simulation techniques to compute various potentials of mean force (PMFs) relevant to protegrin membrane association. These simulations consist of fully atomistic representations of solvated peptide-membrane systems, in which different reaction coordinates are constrained. In the case of peptide adsorption, the relevant reaction coordinate is simply the distance between the peptide and the membrane; the resulting PMF represents the free energy of the system as a function of this distance. The details of these methods are largely omitted here, and the interested reader is referred to [12,13]. Figure 2 below shows the PMF for monomer and dimer adsorption; PMFs for dimerization in different environments are shown in [13].


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

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

PMFs of adsorption for protegrin monomers and dimers on 1:3 POPE:POPG lipid bilayers. D is the separation distance between the PG-1 center of mass and the phosphate plane of the upper leaflet of the membrane. From [12] with permission.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f2-ijms-13-11000: PMFs of adsorption for protegrin monomers and dimers on 1:3 POPE:POPG lipid bilayers. D is the separation distance between the PG-1 center of mass and the phosphate plane of the upper leaflet of the membrane. From [12] with permission.
Mentions: The study of protein-membrane systems by experimental techniques is cumbersome due to the extremely fast time scales and small length scales of the relevant physical phenomena. To address these shortcomings, we have carried out molecular dynamics (MD) simulations coupled to free energy simulation techniques to compute various potentials of mean force (PMFs) relevant to protegrin membrane association. These simulations consist of fully atomistic representations of solvated peptide-membrane systems, in which different reaction coordinates are constrained. In the case of peptide adsorption, the relevant reaction coordinate is simply the distance between the peptide and the membrane; the resulting PMF represents the free energy of the system as a function of this distance. The details of these methods are largely omitted here, and the interested reader is referred to [12,13]. Figure 2 below shows the PMF for monomer and dimer adsorption; PMFs for dimerization in different environments are shown in [13].

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