Modeling the Protective Role of Bacterial Lipopolysaccharides against Membrane-Rupturing Peptides

Nourbakhsh, Shokoofeh; Liu, Yu; Ha, Bae‐Yeun

doi:10.1021/acs.jpcb.1c02330

Cited by 5 publications

(6 citation statements)

References 72 publications

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“…The reason for this is that when LPS molecules are included in the membranes, the size of the system and timescale needed for system equilibration becomes too large for the system to be tractable for MD simulation with a model with all atom resolution. Theoretical studies have, however, been carried out that indicate LPS plays a protective role against antibacterial peptides, e.g., magainin [845].…”

Section: A Clear Case Of Drug Membrane Interaction As Mechanism Of Action-antimicrobial Agentsmentioning

confidence: 99%

Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design

2021

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We review the use of molecular dynamics (MD) simulation as a drug design tool in the context of the role that the lipid membrane can play in drug action, i.e., the interaction between candidate drug molecules and lipid membranes. In the standard “lock and key” paradigm, only the interaction between the drug and a specific active site of a specific protein is considered; the environment in which the drug acts is, from a biophysical perspective, far more complex than this. The possible mechanisms though which a drug can be designed to tinker with physiological processes are significantly broader than merely fitting to a single active site of a single protein. In this paper, we focus on the role of the lipid membrane, arguably the most important element outside the proteins themselves, as a case study. We discuss work that has been carried out, using MD simulation, concerning the transfection of drugs through membranes that act as biological barriers in the path of the drugs, the behavior of drug molecules within membranes, how their collective behavior can affect the structure and properties of the membrane and, finally, the role lipid membranes, to which the vast majority of drug target proteins are associated, can play in mediating the interaction between drug and target protein. This review paper is the second in a two-part series covering MD simulation as a tool in pharmaceutical research; both are designed as pedagogical review papers aimed at both pharmaceutical scientists interested in exploring how the tool of MD simulation can be applied to their research and computational scientists interested in exploring the possibility of a pharmaceutical context for their research.

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Section: A Clear Case Of Drug Membrane Interaction As Mechanism Of Action-antimicrobial Agentsmentioning

confidence: 99%

Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design

2021

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“…Cationic AMPs are attracted to the negatively charged LPS present in the OM of Gram-negative bacteria. 39 Here, pre-incubation of the peptides with LPS reduced their antibacterial activity, suggesting that the peptides bind to the LPS of Psa. Peptide treatment induced the permeabilization of the OM of Psa, and a prominent increase in the fluorescence intensity of nonpermeability fluorescent dye NPN was observed.…”

Section: Discussionmentioning

confidence: 83%

“…The OM of Gram‐negative bacteria plays a crucial role as a physical protective barrier. Cationic AMPs are attracted to the negatively charged LPS present in the OM of Gram‐negative bacteria 39 . Here, pre‐incubation of the peptides with LPS reduced their antibacterial activity, suggesting that the peptides bind to the LPS of Psa .…”

Section: Discussionmentioning

confidence: 90%

Antibacterial mechanism of the novel antimicrobial peptide Jelleine‐Ic and its efficacy in controlling Pseudomonas syringae pv. actinidiae in kiwifruit

Zhang

Wang

Tang

et al. 2023

Pest Management Science

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BACKGROUNDBacterial canker caused by Pseudomonas syringae pv. actinidiae (Psa) poses a severe threat to kiwifruit production. Because of the insufficient efficacy and environmental safety of available treatments, novel antibacterial agents should be urgently developed. Antimicrobial peptides (AMPs) can be used as antimicrobials for disease control. In this study, we designed a novel AMP, Jelleine‐Ic, and evaluated its antibacterial activity and mechanism of action against Psa.RESULTSJelleine‐Ic with a half‐maximal effective concentration of 1.67 μg/mL exhibited stronger antibacterial activity than did parent Jelleine‐I. Jelleine‐Ic targeted the Psa membrane, increased membrane permeabilization and dissipated membrane potential, resulting in calcium leakage. Electron microscopy revealed that Jelleine‐Ic disrupted cell morphology and caused intracellular alterations. Moreover, this AMP penetrated the cell membrane, bound to DNA, and reduced the expression of genes related to DNA replication and repair. Jelleine‐Ic also reduced esterase activity and induced intracellular reactive oxygen species generation. This peptide inhibited the development of Psa canker. The control efficiency of Jelleine‐Ic against Psa in the leaf discs and leaves of kiwifruit was 81.83% and 70.53%, respectively, which was superior to that of the commercial agricultural streptomycin. Furthermore, Jelleine‐Ic upregulated the expression of kiwifruit defense genes (PR‐10 and WRKY70a).CONCLUSIONJelleine‐Ic effectively controls Psa in vitro and in vivo, and may be developed as a bactericide for plant disease control. © 2023 Society of Chemical Industry.

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“…At equilibrium, the local concentration of colloids in the brush is proportional to the Boltzmann factor provided their concentration is small enough to neglect their mutual interactions. The pre-factor is determined by the concentration in the bulk solvent, c 0 , such that c eq (z) = c 0 e −ΔF(z) (10) The ratio between the average colloid concentration in the brush at equilibrium, 〈c eq 〉, and the bulk concentration, defines the average partition coefficient…”

Section: Colloid Insertion Free Energy and Equilibrium Partitioning I...mentioning

confidence: 99%

“…Similarly, a coating rich in lipopolysaccharides helps to protect gram-negative bacteria against antibiotics and antimicrobial peptides. [10] Selective binding and transport is also desirable for technological applications. In particular, polymer brushes can be envisaged as a selective barrier in biosensor applications, [11] by preventing the access of undesired molecules and/or facilitating access of the desired agent, to the biosensor surface thus enhancing biosensor selectivity and/or sensitivity.…”

Section: Introductionmentioning

confidence: 99%

Selective Colloid Transport across Planar Polymer Brushes

Laktionov

Zhulina

Klushin

et al. 2023

Macromol. Rapid Commun.

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Polymer brushes are attractive as surface coatings for a wide range of applications, from fundamental research to everyday life, and also play important roles in biological systems. How colloids (e.g., functional nanoparticles, proteins, viruses) bind and move across polymer brushes is an important yet under‐studied problem. A mean‐field theoretical approach is presented to analyze the binding and transport of colloids in planar polymer brushes. The theory explicitly considers the effect of solvent strength on brush conformation and of colloid‐polymer affinity on colloid binding and transport. The position‐dependent free energy of the colloid insertion into the polymer brush which controls the rate of colloid transport across the brush is derived. It is shown how the properties of the brush can be adjusted for brushes to be highly selective, effectively serving as tuneable gates with respect to colloid size and affinity to the brush‐forming polymer. The most important parameter regime simultaneously allowing for high brush permeability and selectivity corresponds to a condition when the repulsive and attractive contributions to the colloid insertion free energy nearly cancel. This theory should be useful to design sensing and purification devices with enhanced selectivity and to better understand mechanisms underpinning the functions of biological polymer brushes.

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Modeling the Protective Role of Bacterial Lipopolysaccharides against Membrane-Rupturing Peptides

Cited by 5 publications

References 72 publications

Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design

Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design

Antibacterial mechanism of the novel antimicrobial peptide Jelleine‐Ic and its efficacy in controlling Pseudomonas syringae pv. actinidiae in kiwifruit

Selective Colloid Transport across Planar Polymer Brushes

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