Peptide-induced membrane curvature in edge-stabilized open bilayers: A theoretical and molecular dynamics study

Pannuzzo, Martina; Raudino, Antonio; Böckmann, Rainer A.

doi:10.1063/1.4885340

Cited by 17 publications

(20 citation statements)

References 77 publications

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“…Earlier coarse-grained studies on the adsorption or aggregation of proteins on membrane interfaces used nonpolarizable water. ,, Here, we compared both Martini water models for the adsorption of the amphiphatic peptides E and K to a phospholipid bilayer.…”

Section: Resultsmentioning

confidence: 99%

Spontaneous Adsorption of Coiled-Coil Model Peptides K and E to a Mixed Lipid Bilayer

et al. 2015

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A molecular description of the lipid-protein interactions underlying the adsorption of proteins to membranes is crucial for understanding, for example, the specificity of adsorption or the binding strength of a protein to a bilayer, or for characterizing protein-induced changes of membrane properties. In this paper, we extend an automated in silico assay (DAFT) for binding studies and apply it to characterize the adsorption of the model fusion peptides E and K to a mixed phospholipid/cholesterol membrane using coarse-grained molecular dynamics simulations. In addition, we couple the coarse-grained protocol to reverse transformation to atomistic resolution, thereby allowing to study molecular interactions with high detail. The experimentally observed differential binding of the peptides E and K to membranes, as well as the increased binding affinity of helical over unstructered peptides, could be well reproduced using the polarizable Martini coarse-grained (CG) force field. Binding to neutral membranes is shown to be dominated by initial binding of the positively charged N-terminus to the phospholipid headgroup region, followed by membrane surface-aligned insertion of the peptide at the interface between the hydrophobic core of the membrane and its polar headgroup region. Both coarse-grained and atomistic simulations confirm a before hypothesized snorkeling of lysine side chains for the membrane-bound state of the peptide K. Cholesterol was found to be enriched in peptide vicinity, which is probably of importance for the mechanism of membrane fusion. The applied sequential multiscale method, using coarse-grained simulations for the slow adsorption process of peptides to membranes followed by backward transformation to atomistic detail and subsequent atomistic simulations of the preformed peptide-lipid complexes, is shown to be a versatile approach to study the interactions of peptides or proteins with biomembranes.

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Section: Resultsmentioning

confidence: 99%

Spontaneous Adsorption of Coiled-Coil Model Peptides K and E to a Mixed Lipid Bilayer

et al. 2015

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“…537 The extent of curvature induction was found to depend sensitively on the molecular interactions and cannot be explained using simple shape-based concepts. Pannuzzo et al 538 proposed an efficient approach to simulate the bending power of peptides based on the use of lipid bicelles that are stabilized by short-chain lipids.…”

Section: Increasing Complexitymentioning

confidence: 99%

Computational Modeling of Realistic Cell Membranes

Marrink¹,

Corradi

Souza³

et al. 2019

Chem. Rev.

585

488

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Cell membranes contain a large variety of lipid types and are crowded with proteins, endowing them with the plasticity needed to fulfill their key roles in cell functioning. The compositional complexity of cellular membranes gives rise to a heterogeneous lateral organization, which is still poorly understood. Computational models, in particular molecular dynamics simulations and related techniques, have provided important insight into the organizational principles of cell membranes over the past decades. Now, we are witnessing a transition from simulations of simpler membrane models to multicomponent systems, culminating in realistic models of an increasing variety of cell types and organelles. Here, we review the state of the art in the field of realistic membrane simulations and discuss the current limitations and challenges ahead.

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“…Membrane curvature is in silico most effectively studied in CG MD simulations of a metastable finite bilayer patch that minimizes the suppression of curved structures in the typically employed periodic setups and also allows for vesicle formation (66). A peptide-free bilayer patch (DOPC: DOPE:cholesterol 2:1:1, in total 1150 molecules, Fig.…”

Section: Peptide K Promotes Positive Curvature In Coarse-grained MD Smentioning

confidence: 99%

A Coiled-Coil Peptide Shaping Lipid Bilayers upon Fusion

Rabe

Aisenbrey

Pluháčková

et al. 2016

Biophysical Journal

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A system based on two designed peptides, namely the cationic peptide K, (KIAALKE) 3 , and its complementary anionic counterpart called peptide E, (EIAALEK) 3 , has been used as a minimal model for membrane fusion, inspired by SNARE proteins. Although the fact that docking of separate vesicle populations via the formation of a dimeric E/K coiled-coil complex can be rationalized, the reasons for the peptides promoting fusion of vesicles cannot be fully explained. Therefore it is of significant interest to determine how the peptides aid in overcoming energetic barriers during lipid rearrangements leading to fusion. In this study, investigations of the peptides' interactions with neutral PC/PE/cholesterol membranes by fluorescence spectroscopy show that tryptophan-labeled K* binds to the membrane (K K*~6 .2 10 3 M À1 ), whereas E* remains fully water-solvated. 15 N-NMR spectroscopy, depth-dependent fluorescence quenching, CD-spectroscopy experiments, and MD simulations indicate a helix orientation of K* parallel to the membrane surface. Solid-state 31 P-NMR of oriented lipid membranes was used to study the impact of peptide incorporation on lipid headgroup alignment. The membrane-immersed K* is found to locally alter the bilayer curvature, accompanied by a change of headgroup orientation relative to the membrane normal and of the lipid composition in the vicinity of the bound peptide. The NMR results were supported by molecular dynamics simulations, which showed that K reorganizes the membrane composition in its vicinity, induces positive membrane curvature, and enhances the lipid tail protrusion probability. These effects are known to be fusion relevant. The combined results support the hypothesis for a twofold role of K in the mechanism of membrane fusion: 1) to bring opposing membranes into close proximity via coiled-coil formation and 2) to destabilize both membranes thereby promoting fusion.

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Peptide-induced membrane curvature in edge-stabilized open bilayers: A theoretical and molecular dynamics study

Cited by 17 publications

References 77 publications

Spontaneous Adsorption of Coiled-Coil Model Peptides K and E to a Mixed Lipid Bilayer

Spontaneous Adsorption of Coiled-Coil Model Peptides K and E to a Mixed Lipid Bilayer

Computational Modeling of Realistic Cell Membranes

A Coiled-Coil Peptide Shaping Lipid Bilayers upon Fusion

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