Accelerated molecular dynamics simulation analysis of MSI-594 in a lipid bilayer

Mukherjee, Subrata; Kar, Rup Kumar; Nanga, Ravi Prakash Reddy; Mroué, Kamal H.; Ramamoorthy, Ayyalusamy; Bhunia, Anirban

doi:10.1039/c7cp01941f

Cited by 47 publications

(59 citation statements)

References 60 publications

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“…To investigate the effect of the lipid composition, various ratios of POPC and POPG were evaluated. Whereas POPS can be used to mimic the negative net charge of bacterial membranes, POPG is a more common lipid in bacterial membranes 22 . At a ratio of POPC:POPG (95:5) the lipid membrane was slightly more resilient to perturbation by L-PLNC8 αβ compared to POPS containing lipid membranes, requiring a peptide concentration of 0.7 µM to reach 50% CF-release ( Fig.…”

Section: Antimicrobial Activity Of Native L-and D-plnc8 αβmentioning

confidence: 99%

Plantaricin NC8 αβ exerts potent antimicrobial activity against Staphylococcus spp. and enhances the effects of antibiotics

Bengtsson

Selegård

Musa

et al. 2020

Sci Rep

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The use of conventional antibiotics has substantial clinical efficacy, however these vital antimicrobial agents are becoming less effective due to the dramatic increase in antibiotic-resistant bacteria. Novel approaches to combat bacterial infections are urgently needed and bacteriocins represent a promising alternative. In this study, the activities of the two-peptide bacteriocin PLNC8 αβ were investigated against different Staphylococcus spp. The peptide sequences of PLNC8 α and β were modified, either through truncation or replacement of all L-amino acids with D-amino acids. Both Land D-PLNC8 αβ caused rapid disruption of lipid membrane integrity and were effective against both susceptible and antibiotic resistant strains. the D-enantiomer was stable against proteolytic degradation by trypsin compared to the L-enantiomer. Of the truncated peptides, β1-22, β7-34 and β1-20 retained an inhibitory activity. The peptides diffused rapidly (2 min) through the bacterial cell wall and permeabilized the cell membrane, causing swelling with a disorganized peptidoglycan layer. Interestingly, sub-MIC concentrations of PLNC8 αβ substantially enhanced the effects of different antibiotics in an additive or synergistic manner. This study shows that PLNC8 αβ is active against Staphylococcus spp. and may be developed as adjuvant in combination therapy to potentiate the effects of antibiotics and reduce their overall use. Although antibiotics are the most effective treatment against bacteria of the genus Staphylococcus (including the species S. aureus and S. epidermidis), these opportunistic pathogens are one of the leading causes of severe bacterial infections in humans connected to chronic wounds and medical devices, e.g. catheters and prosthetic implants 1. These persistent infections are generally difficult to treat, which increases the risk for bacterial dissemination and development of systemic complications 2,3. Furthermore, considering the gradual increase in antimicrobial resistance, treatment may be even more difficult to achieve as the available options become limited 4. Consequently, there is an urgent need to find new approaches in human medicine against bacterial infections, and bacteriocins represent a promising avenue that requires more consideration 5,6. Bacteriocins are antimicrobial peptides that are produced by most microorganisms that contribute their defence mechanisms. These peptides are divided into class I-V based on their structural characteristics. Class I includes small peptides (<5 kDa) with unusual amino acids, such as lanthionine and β-methyllanthionine that are post-translationally introduced and class II peptides are synthesized in precursor forms and processed (<10 kDa), and includes bacteriocins composed of two peptides (class IIb), such as PLNC8 αβ. Class III bacteriocins are large (>10 kDa) and sensitive to heat, class IV are small (<10 kDa) and circular peptides. Class V are small (<5 kDa), circular or linear peptides that are characterized by containing cross-linkages between cysteine residu...

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Section: Antimicrobial Activity Of Native L-and D-plnc8 αβmentioning

confidence: 99%

Plantaricin NC8 αβ exerts potent antimicrobial activity against Staphylococcus spp. and enhances the effects of antibiotics

Bengtsson

Selegård

Musa

et al. 2020

Sci Rep

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“…Structural stabilization occurred around 50 ns. In this model for Gram-negative bacteria in absence of peptides, with molar ratio POPG/POPE 1:3, the published values of area per lipid (Å 2 ) and membrane thickness (Å) was found to be 58.34 ± 1.33 and 41.65 ± 0.78, respectively [16]. The values obtained from our MD simulations were 57.7 ± 0.7 and 42.17 ± 0.3 for same parameters.…”

Section: Resultsmentioning

confidence: 99%

“…The lipid bilayer model were constructed for the theoretical study with the purpose of simulating the Gram negative membranes from bacteria. To construct this model, a mixture with a 1:3 molar ratio of anionic 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG) to 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE) was used [16]. The Membrane Builder module of the CHARMM-GUI [33] server was used for the construction of lipid bilayers.…”

Section: Methodsmentioning

confidence: 99%

Potent and Broad-Spectrum Antimicrobial Activity of Analogs from the Scorpion Peptide Stigmurin

Amorim-Carmo

Daniele-Silva

Parente

et al. 2019

IJMS

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Scorpion venom constitutes a rich source of biologically active compounds with high potential for therapeutic and biotechnological applications that can be used as prototypes for the design of new drugs. The aim of this study was to characterize the structural conformation, evaluate the antimicrobial activity, and gain insight into the possible action mechanism underlying it, for two new analog peptides of the scorpion peptide Stigmurin, named StigA25 and StigA31. The amino acid substitutions in the native sequence for lysine residues resulted in peptides with higher positive net charge and hydrophobicity, with an increase in the theoretical helical content. StigA25 and StigA31 showed the capacity to modify their structural conformation according to the environment, and were stable to pH and temperature variation—results similar to the native peptide. Both analog peptides demonstrated broad-spectrum antimicrobial activity in vitro, showing an effect superior to that of the native peptide, being non-hemolytic at the biologically active concentrations. Therefore, this study demonstrates the therapeutic potential of the analog peptides from Stigmurin and the promising approach of rational drug design based on scorpion venom peptide to obtain new anti-infective agents.

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“…Pardaxin is an AMP with high antibacterial activities; we also aimed to investigate the effects of the peptide on the bacterial model membranes. Therefore, we have also selected two models of the membrane including 1-palmitoyl-2-oleoyl-phosphatidylglycerol/1-palmitoyl-2-oleoyl phosphatidylethanolamine (POPG/POPE) with a ratio of 3:1 (a model for the gram-negative bacteria) and POPE/POPG with a ratio of 1:3 (a model for gram-positive bacteria) [ 42 , 43 ]. We investigated the structural and dynamical changes of the peptide, the pardaxin-bilayer interactions in detail, and the membrane responses to the peptide.…”

Section: Introductionmentioning

confidence: 99%

Insight into the interactions, residue snorkeling, and membrane disordering potency of a single antimicrobial peptide into different lipid bilayers

2017

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Pardaxin, with a bend-helix-bend-helix structure, is a membrane-active antimicrobial peptide that its membrane activity depends on the lipid bilayer composition. Herein, all-atom molecular dynamics (MD) simulations were performed to provide further molecular insight into the interactions, structural dynamics, orientation behavior, and cationic residues snorkeling of pardaxin in the DMPC, DPPC, POPC, POPG, POPG/POPE (3:1), and POPG/POPE (1:3) lipid bilayers. The results showed that the C-terminal helix of the peptide was maintained in all six types of the model-bilayers and pardaxin was tilted into the DMPC, DPPC, and POPG/POPE mixed bilayers more than the POPC and POPG bilayers. As well as, the structure of zwitterionic membranes was more affected by the peptide than the anionic bilayers. Taken together, the study demonstrated that the cationic residues of pardaxin snorkeled toward the interface of lipid bilayers and all phenylalanine residues of the peptide played important roles in the peptide-membrane interactions. We hope that this work will provide a better understanding of the interactions of antimicrobial peptides with the membranes.

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Accelerated molecular dynamics simulation analysis of MSI-594 in a lipid bilayer

Cited by 47 publications

References 60 publications

Plantaricin NC8 αβ exerts potent antimicrobial activity against Staphylococcus spp. and enhances the effects of antibiotics

Plantaricin NC8 αβ exerts potent antimicrobial activity against Staphylococcus spp. and enhances the effects of antibiotics

Potent and Broad-Spectrum Antimicrobial Activity of Analogs from the Scorpion Peptide Stigmurin

Insight into the interactions, residue snorkeling, and membrane disordering potency of a single antimicrobial peptide into different lipid bilayers

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