scholarly journals Magainin 2 and PGLa in Bacterial Membrane Mimics II: Membrane Fusion and Sponge Phase Formation

2019 ◽  
Author(s):  
Ivo Kabelka ◽  
Michael Pachler ◽  
Sylvain Prévost ◽  
Ilse Letofsky-Papst ◽  
Karl Lohner ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Defect Formation ◽  
Preceding Paper ◽  
Lipid Vesicles ◽  
Synergistic Activity ◽  
Electron Microscopic ◽  
Synergistic Mechanism ◽  
Sponge Phase ◽  
Lipid Aggregates ◽  
Dynamics Simulations

ABSTRACTWe studied the synergistic mechanism of equimolar mixtures of magainin 2 (MG2a) and PGLa in phosphatidylethanolamine/phosphatidylglycerol mimics of Gram-negative cytoplasmic membranes. In a preceding paper [Pachler et al., Biophys. J. 2019 xxx], we reported on the early onset of parallel heterodimer formation of the two antimicrobial peptides already at low concentrations and the resulting defect formation in membranes. Here, we focus on the structures of the peptide/lipid aggregates occurring in the synergistic regime at elevated peptide concentrations. Using a combination of calorimetric, scattering, electron microscopic and in silico techniques, we demonstrate that the two peptides, even if applied individually, transform originally large unilamellar vesicles into multilamellar vesicles, with a collapsed interbilayer spacing resulting from peptide induced adhesion. Interestingly, the adhesion does not lead to a peptide induced lipid separation of charged and charge neutral species. In addition to this behavior, equimolar mixtures of MG2a and PGLa formed surface-aligned fibril-like structures, which induced adhesion zones between the membranes and the formation of transient fusion stalks in molecular dynamics simulations and a coexisting sponge phase observed by small-angle X-ray scattering. The previously reported increased leakage of lipid vesicles of identical composition in the presence of MG2a/PGLa mixtures is therefore related to a peptide-induced cross-linking of bilayers.STATEMENT OF SIGNIFICANCEWe demonstrate that the synergistic activity of the antimicrobial peptides MG2a and PGLa correlates to the formation of surface-aligned fibril-like peptide aggregates, which cause membrane adhesion, fusion and finally the formation of a sponge phase.

scholarly journals Magainin 2 and PGLa in Bacterial Membrane Mimics I: Peptide-Peptide and Lipid-Peptide Interactions

2019 ◽  
Author(s):  
Michael Pachler ◽  
Ivo Kabelka ◽  
Marie-Sousai Appavou ◽  
Karl Lohner ◽  
Robert Vácha ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Lipid Vesicles ◽  
Coarse Grained ◽  
Joint Analysis ◽  
Synergistic Activity ◽  
Salt Bridges ◽  
Membrane Perturbation ◽  
High Concentrations ◽  
Dynamics Simulations ◽  
The Individual

ABSTRACTWe addressed the onset of synergistic activity of the two well-studied antimicrobial peptides magainin 2 (MG2a) and PGLa using lipid-only mimics of Gram-negative cytoplasmic membranes. Specifically, we coupled a joint analysis of small-angle X-ray and neutron scattering experiments on fully hydrated lipid vesicles in the presence of MG2a and L18W-PGLa to all-atom and coarse-grained molecular dynamics simulations. In agreement with previous studies both peptides, as well as their equimolar mixture, were found to remain in a surface-aligned topology upon membrane insertion and to induce significant membrane perturbation as evidenced by membrane thinning and hydrocarbon order parameter changes in the vicinity of the inserted peptide. These effects were particularly pronounced for the so called synergistic mixture of 1:1 (mol/mol) L18W-PGLa/MG2a and cannot be accounted for by a linear combination of the membrane perturbations of two peptides individually. Our data are consistent with parallel heterodimers forming at much lower concentrations than previously considered, but which do not induce a synergistic leakage of dyes. Our simulations further show that the heterodimers interact via salt bridges and hydrophobic forces, which apparently makes them more stable than putatively formed antiparallel L18W-PGLa and MG2a homodimers. Moreover, dimerization of L18W-PGLa and MG2a leads to a relocation of the peptides within the lipid headgroup regime as compared to the individual peptides. The early onset of dimerization of L18W-PGLa and MG2a at low peptide concentrations consequently appears to be key to their synergistic dye-releasing activity from lipid vesicles at high concentrations.STATEMENT OF SIGNIFICANCEWe demonstrate that specific interactions of the antimicrobial peptides MG2a and PGLa with each other in POPE/POPG bilayers lead to the formation of surface-aligned parallel dimers, which provide already at low peptide concentrations the nucleus for the peptides’ well-known synergistic activity.

Computational studies of ice defects

2003 ◽  
Vol 81 (1-2) ◽  
pp. 325-332 ◽  
Author(s):  
P LM Plummer
Keyword(s):  
Defect Formation ◽  
Structural Evolution ◽  
Energy Difference ◽  
Electronic Energy ◽  
Energy Structure ◽  
Defect Site ◽  
And Migration ◽  
Dynamics Simulations ◽  
Small Clusters ◽  
Structure Calculations

Continuing our investigations of the energetics associated with defect formation and migration, both ab initio energy-structure calculations and molecular dynamics simulations are carried out on small clusters of water molecules containing one or more defects in hydrogen bonding. Previous studies in this series have identified structures containing defects that are stable at 0 K or that are transition states between such structures. However, results from this laboratory and elsewhere have shown that the energy required for the production or migration of a defect is more complex than merely the energy difference between the static structures. Cooperative motion of neighbors to the defect site can either increase or decrease the energy involved to produce or annihilate the defect. Thus, experimental measurements associated with the energy of defects in ice can differ substantially from those calculated using static models. By increasing the complexity of the model, the studies described in this report attempt to more realistically simulate a defect-containing ice system. The types of defects studied include ion and ion-pair defects. The initial structures are energetically stable — minima on the electronic energy surface — and contain one or more kinds of defects. Since the means and amount of energy injection can alter the migration path, the energy is introduced into the system in a variety of ways. The structural evolution of the ice system is then monitored as a function of time. PACS Nos.: 82.20Wt, 82.20Kh, 82.30Rs

scholarly journals Chromatin remodelers couple inchworm motion with twist-defect formation to slide nucleosomal DNA

2018 ◽  
Author(s):  
Giovanni B. Brandani ◽  
Shoji Takada
Keyword(s):  
Genome Organization ◽  
Electrostatic Interactions ◽  
Defect Formation ◽  
Energy Landscape ◽  
Molecular Machines ◽  
Biological Processes ◽  
Complete Understanding ◽  
Chromatin Remodelers ◽  
Nucleosomal Dna ◽  
Dynamics Simulations

ABSTRACTATP-dependent chromatin remodelers are molecular machines that control genome organization by repositioning, ejecting, or editing nucleosomes, activities that confer them essential regulatory roles on gene expression and DNA replication. Here, we investigate the molecular mechanism of active nucleosome sliding by means of molecular dynamics simulations of the Snf2 remodeler in complex with a nucleosome. During its inchworm motion driven by ATP consumption, the remodeler overwrites the original nucleosome energy landscape via steric and electrostatic interactions to induce sliding of nucleosomal DNA unidirectionally. The sliding is initiated at the remodeler binding location via the generation of twist defects, which then spontaneously propagate to complete sliding throughout the entire nucleosome. We also reveal how remodeler mutations and DNA sequence control active nucleosome repositioning, explaining several past experimental observations. These results offer a detailed mechanistic picture of remodeling important for the complete understanding of these important biological processes.

scholarly journals The Droserasin 1 PSI: A Membrane-Interacting Antimicrobial Peptide from the Carnivorous Plant Drosera capensis

Biomolecules ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 1069
Author(s):  
Marc A. Sprague-Piercy ◽  
Jan C. Bierma ◽  
Marquise G. Crosby ◽  
Brooke P. Carpenter ◽  
Gemma R. Takahashi ◽  
...  
Keyword(s):  
Antimicrobial Peptide ◽  
Disulfide Bonds ◽  
Lipid Vesicles ◽  
Carnivorous Plant ◽  
Nmr Studies ◽  
Biophysical Characterization ◽  
Head Groups ◽  
Wide Range ◽  
Dynamics Simulations ◽  
Lipid Nanodiscs

The Droserasins, aspartic proteases from the carnivorous plant Drosera capensis, contain a 100-residue plant-specific insert (PSI) that is post-translationally cleaved and independently acts as an antimicrobial peptide. PSIs are of interest not only for their inhibition of microbial growth, but also because they modify the size of lipid vesicles and strongly interact with biological membranes. PSIs may therefore be useful for modulating lipid systems in NMR studies of membrane proteins. Here we present the expression and biophysical characterization of the Droserasin 1 PSI (D1 PSI.) This peptide is monomeric in solution and maintains its primarily α -helical secondary structure over a wide range of temperatures and pH values, even under conditions where its three disulfide bonds are reduced. Vesicle fusion assays indicate that the D1 PSI strongly interacts with bacterial and fungal lipids at pH 5 and lower, consistent with the physiological pH of D. capensis mucilage. It binds lipids with a variety of head groups, highlighting its versatility as a potential stabilizer for lipid nanodiscs. Solid-state NMR spectra collected at a field strength of 36 T, using a unique series-connected hybrid magnet, indicate that the peptide is folded and strongly bound to the membrane. Molecular dynamics simulations indicate that the peptide is stable as either a monomer or a dimer in a lipid bilayer. Both the monomer and the dimer allow the passage of water through the membrane, albeit at different rates.

Impact of Molecular Dynamics Simulations on Research and Development of Semiconductor Materials

MRS Advances ◽  
2019 ◽  
Vol 4 (61-62) ◽  
pp. 3381-3398
Author(s):  
Xiaowang Zhou
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Recent Progress ◽  
Defect Formation ◽  
Atomic Scale ◽  
Semiconductor Materials ◽  
Formation Mechanisms ◽  
Graphene Growth ◽  
First Case ◽  
Dynamics Simulations

ABSTRACTAtomic scale defects critically limit performance of semiconductor materials. To improve materials, defect effects and defect formation mechanisms must be understood. In this paper, we demonstrate multiple examples where molecular dynamics simulations have effectively addressed these issues that were not well addressed in prior experiments. In the first case, we report our recent progress on modelling graphene growth, where we found that defects in graphene are created around periphery of islands throughout graphene growth, not just in regions where graphene islands impinge as believed previously. In the second case, we report our recent progress on modelling TlBr, where we discovered that under an electric field, edge dislocations in TlBr migrate in both slip and climb directions. The climb motion ejects extensive vacancies that can cause the rapid aging of the material seen in experiments. In the third case, we discovered that the growth of InGaN films on (0001) surfaces suffers from a serious polymorphism problem that creates enormous amounts of defects. Growth on ($11\bar{2}0$) surfaces, on the other hand, results in single crystalline wurtzite films without any of these defects. In the fourth case, we first used simulations to derive dislocation energies that do not possess any noticeable statistical errors, and then used these error-free methods to discover possible misuse of misfit dislocation theory in past thin film studies. Finally, we highlight the significance of molecular dynamics simulations in reducing defects in the design space of nanostructures.

Sign in / Sign up

Export Citation Format

Share Document