Journal ArticleDOI
Adaptation of a membrane-active peptide to heterogeneous environment. I. Structural plasticity of the peptide.
TLDR
A combined modeling approach is used that includes molecular dynamics simulations of pAntp in zwitterionic and anionic lipid bilayers, free energy perturbation calculations of model residue-residue contacts, and detailed analysis of spatial hydrophobic/hydrophilic properties of the peptide/membrane systems.Abstract:
Some membrane-active peptides undergo drastic changes of conformation and/or orientation on water-lipid interfaces. Among the most notable examples is penetratin (pAntp), a short cell-penetrating peptide. To delineate the driving forces behind pAntp-membrane interactions, we used, in this series of two papers, a combined modeling approach that includes: (1) molecular dynamics simulations of pAntp in zwitterionic and anionic lipid bilayers, (2) free energy perturbation calculations of model residue-residue contacts, and (3) detailed analysis of spatial hydrophobic/hydrophilic properties of the peptide/membrane systems. In this first article, we consider the role of conformational plasticity of the peptide in different membrane surroundings, as well as the ability of pAntp to form stable specific residue-residue interactions and make contacts with particular lipids. It was shown that pAntp displays a complicated conformational behavior. Basic and aromatic residues of the peptide form energetically favorable pairs in water and apolar environments, which facilitate membrane insertion of the peptide and stabilization of the membrane-bound state. These residues are also capable of "trapping" lipid heads, thereby affecting their dynamics and microscopic organization of the water-lipid interface. The latter effect is much more pronounced in anionic bilayers and might be related to the initial stage of peptide-induced destabilization of lipid bilayers.read more
Citations
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Journal ArticleDOI
Secondary structure of cell-penetrating peptides controls membrane interaction and insertion.
TL;DR: A comparative analysis of the structural plasticity of 10 well-known CPPs as well as their ability to interact with phospholipid membranes is reported, and a new classification of C PPs is proposed based on their structural properties, affinity for phospholIPids and internalization pathways already reported in the literature.
Journal ArticleDOI
The role of spontaneous lipid curvature in the interaction of interfacially active peptides with membranes
Daniel Koller,Karl Lohner +1 more
TL;DR: Different parameters such as H-bonding, electrostatic repulsion, changes in monolayer surface area and lateral pressure that affect induction of membrane curvature, but also vice versa how membranes curvature triggers peptide response are discussed.
Journal ArticleDOI
Cell biology meets biophysics to unveil the different mechanisms of penetratin internalization in cells
Isabel D. Alves,Chen-Yu Jiao,Soline Aubry,Baptiste Aussedat,Fabienne Burlina,Gérard Chassaing,Sandrine Sagan +6 more
TL;DR: This review will focus solely on penetratin membrane interactions and internalization mechanisms and suggests that different translocation mechanisms could co-exist, an idea that emerges from recent studies.
Journal ArticleDOI
Antimicrobial Peptides Induce Growth of Phosphatidylglycerol Domains in a Model Bacterial Membrane
Anton A. Polyansky,Anton A. Polyansky,Rajesh Ramaswamy,Pavel E. Volynsky,Ivo F. Sbalzarini,Siewert J. Marrink,Roman G. Efremov +6 more
TL;DR: The presence of AMPs systematically affects the dynamics and induces long-range order in the structure of PG domains, stabilizing the separation between the two lipid fractions, and providing a possible explanation for the multimodal character of AMP activity.
Journal ArticleDOI
One-month subchronic toxicity study of cell-penetrating peptides for insulin nasal delivery in rats.
El-Sayed Khafagy,El-Sayed Khafagy,Noriyasu Kamei,Ebbe Juel Bech Nielsen,Ebbe Juel Bech Nielsen,Reiji Nishio,Mariko Takeda-Morishita +6 more
TL;DR: Investigation of the bioavailability of insulin and the adverse effects on the nasal mucosa in rats following a long-term dosing regimen of L-penetratin and the novel penetratin analogue "PenetraMax" finds that PenetraMax, a novel CPP candidate, can open a new avenue in clinical trials for noninvasive nasal insulin delivery.
References
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Journal ArticleDOI
Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features
Wolfgang Kabsch,Chris Sander +1 more
TL;DR: A set of simple and physically motivated criteria for secondary structure, programmed as a pattern‐recognition process of hydrogen‐bonded and geometrical features extracted from x‐ray coordinates is developed.
Journal ArticleDOI
GROMACS: Fast, flexible, and free
David van der Spoel,Erik Lindahl,Berk Hess,Gerrit Groenhof,Alan E. Mark,Herman J. C. Berendsen +5 more
TL;DR: The software suite GROMACS (Groningen MAchine for Chemical Simulation) that was developed at the University of Groningen, The Netherlands, in the early 1990s is described, which is a very fast program for molecular dynamics simulation.
Journal ArticleDOI
Development and Testing of the OPLS All-Atom Force Field on Conformational Energetics and Properties of Organic Liquids
TL;DR: In this article, the parametrization and testing of the OPLS all-atom force field for organic molecules and peptides are described, and the parameters for both torsional and non-bonded energy properties have been derived, while the bond stretching and angle bending parameters have been adopted mostly from the AMBER force field.
Journal ArticleDOI
Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria?
TL;DR: In this review the different models of antimicrobial-peptide-induced pore formation and cell killing are presented and several observations suggest that translocated peptides can alter cytoplasmic membrane septum formation, inhibit cell-wall synthesis, inhibit nucleic-acid synthesis, inhibits protein synthesis or inhibit enzymatic activity.
Journal ArticleDOI
The third helix of the Antennapedia homeodomain translocates through biological membranes
TL;DR: It is reported here that a polypeptide of 16 amino acids in length corresponding to the third helix of the homeodomain deleted of its N-terminal glutamate is still capable of translocating through the membrane, suggesting an energy-independent mechanism of translocation not involving classical endocytosis.