375 results on '"Siewert J. Marrink"'
Search Results
202. Computational Modeling of Realistic Cell Membranes
- Author
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Siewert J. Marrink
- Subjects
medicine.anatomical_structure ,Membrane ,Chemistry ,Cell ,Biophysics ,medicine - Published
- 2018
203. Lipid Organization in Simulations of Cell Membranes
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Siewert J. Marrink, Svetlana Baoukina, D. Peter Tieleman, and Helgi I. Ingólfsson
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Membrane ,medicine.anatomical_structure ,Chemistry ,Cell ,Biophysics ,medicine - Published
- 2018
204. Microscopic View on Non-viral Mediated Transfection
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Bart M H Bruininks, Paulo C. T. Souza, Siewert J. Marrink, and Molecular Dynamics
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Chemistry ,Biophysics ,Transfection ,Cell biology - Published
- 2018
205. Molecular Dynamcis of Light-Harvesting Complex II Embedded in the Thylakoid Membrane
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Petteri A. Vainikka, Sebastian Thallmair, Siewert J. Marrink, and Molecular Dynamics
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0303 health sciences ,03 medical and health sciences ,0302 clinical medicine ,Chemistry ,Thylakoid ,Biophysics ,030217 neurology & neurosurgery ,030304 developmental biology ,Light harvesting complex II - Published
- 2018
206. Lipid-mediated interactions tune the association of glycophorin A helix and its disruptive mutants in membranes
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Durba Sengupta, Siewert J. Marrink, Groningen Biomolecular Sciences and Biotechnology, Zernike Institute for Advanced Materials, and Molecular Dynamics
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MOLECULAR-DYNAMICS SIMULATIONS ,Amino Acid Motifs ,Mutant ,General Physics and Astronomy ,Plasma protein binding ,Molecular Dynamics Simulation ,Protein Structure, Secondary ,Protein structure ,Glycophorin ,Glycophorins ,Physical and Theoretical Chemistry ,Lipid bilayer ,DIMERIZATION MOTIF ,DIMER ,biology ,Chemistry ,Cell Membrane ,Wild type ,Biological membrane ,PROTEIN STRUCTURE ,FREE-ENERGY ,Lipids ,SELF-ASSOCIATION ,Transmembrane domain ,HYDROPHOBIC MISMATCH ,Amino Acid Substitution ,Biochemistry ,Mutation ,Biophysics ,biology.protein ,FORCE-FIELD ,Dimerization ,TRANSMEMBRANE ALPHA-HELICES ,Protein Binding ,BIOLOGICAL MEMBRANE - Abstract
The specific and non-specific driving forces of helix association within membranes are still poorly understood. Here, we use coarse-grain molecular dynamics simulations to study the association behavior of glycophorin A and two disruptive mutants, T87F and a triple mutant of the GxxxG motif (G79LG83LG86L), embedded in a lipid membrane. Self-assembly simulations and the association free-energy profile confirm an energetically-favorable dimerized state for both the wild type and the mutants. The reduced association of the mutants compared to the wild type, as observed in experiments, can be justified from comparisons of the free energy profiles. Less-favorable protein-protein interactions as well as disruption of lipid packing around the mutant dimers is responsible for their reduced association. The role of the non-specific "lipid-phobic'' contribution appears to be as important as the specific "helix-helix'' contribution. However, the differences between the wild type and mutants are subtle and our simulations predict a dimerization state not only for the wild-type glycophorin A, but also for these 'disruptive' mutants. Our results highlight the importance of both specific as well as non-specific driving forces in the association of transmembrane helices, and point to the need of more careful interpretation of experimental measurements.
- Published
- 2010
207. Lateral pressure profiles in lipid monolayers
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Siewert J. Marrink, D. Peter Tieleman, Svetlana Baoukina, Groningen Biomolecular Sciences and Biotechnology, Zernike Institute for Advanced Materials, Molecular Dynamics, and Faculty of Science and Engineering
- Subjects
MECHANISM ,Phase transition ,MOLECULAR-DYNAMICS SIMULATIONS ,1,2-Dipalmitoylphosphatidylcholine ,Lipid composition ,Molecular Dynamics Simulation ,LANGMUIR MONOLAYER ,01 natural sciences ,Phase Transition ,Surface tension ,03 medical and health sciences ,Molecular dynamics ,BILAYER-MEMBRANES ,Pulmonary surfactant ,0103 physical sciences ,Monolayer ,Pressure ,Surface Tension ,Physical and Theoretical Chemistry ,COMPUTER-SIMULATIONS ,Lipid bilayer ,030304 developmental biology ,PROTEIN FUNCTION ,0303 health sciences ,Protein function ,Chromatography ,010304 chemical physics ,Chemistry ,CHOLESTEROL ,MODEL ,Chemical physics ,FORCE-FIELD ,LUNG SURFACTANT - Abstract
We have used molecular dynamics simulations with coarse-grained and atomistic models to study the lateral pressure profiles in lipid monolayers. We first consider simple oil/air and oil/water interfaces, and then proceed to lipid monolayers at air/water and oil/water interfaces. The results are qualitatively similar in both atomistic and coarse-grained models. The lateral pressure profile in a monolayer is characterized by a headgroup/water pressure-interfacial tension-chain pressure pattern. In contrast to lipid bilayers, the pressure decreases towards the chain free ends. An additional chain/air tension peak is present in monolayers at the air/water interface. Lateral pressure profiles are calculated for monolayers of different lipid composition under varying surface tension. Increasing the surface tension suppresses both pressure peaks and widens the interfacial tension in monolayers at the oil/water interface, and mainly suppresses the chain pressure in monolayers at the air/water interface. In monolayers in the liquid-condensed phase, the pressure peaks split due to ordering. Variation of lipid composition leads to noticeable changes in all regions of the pressure profile at a fixed surface tension.
- Published
- 2010
208. Membrane poration by antimicrobial peptides combining atomistic and coarse-grained descriptions
- Author
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Andrzej J. Rzepiela, Durba Sengupta, Siewert J. Marrink, Nicolae Goga, Groningen Biomolecular Sciences and Biotechnology, Zernike Institute for Advanced Materials, Molecular Dynamics, and Faculty of Science and Engineering
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MOLECULAR-DYNAMICS SIMULATIONS ,Antimicrobial peptides ,Molecular Sequence Data ,MAGAININ 2 ,Melittin ,Protein Structure, Secondary ,chemistry.chemical_compound ,Membrane Lipids ,LIPID-BILAYER ,Protein structure ,Computational chemistry ,MELITTIN ,FLIP-FLOP ,Computer Simulation ,Amino Acid Sequence ,Physical and Theoretical Chemistry ,Lipid bilayer ,Transmembrane protein ,TRANSLOCATION ,MODEL ,PHOSPHOLIPIDS ,Membrane ,chemistry ,Chemical physics ,PORE FORMATION ,FORCE-FIELD ,Antimicrobial Cationic Peptides - Abstract
Antimicrobial peptides (AMPs) comprise a large family of peptides that include small cationic peptides, such as magainins, which permeabilize lipid membranes. Previous atomistic level simulations of magainin-H2 peptides show that they act by forming toroidal transmembrane pores. However, due to the atomistic level of description, these simulations were necessarily limited to small system sizes and sub-microsecond time scales. Here, we study the long-time relaxation properties of these pores by evolving the systems using a coarse-grain (CG) description. The disordered nature and the topology of the atomistic pores are maintained at the CG level. The peptides sample different orientations but at any given time, only a few peptides insert into the pore. Key states observed at the CG level are subsequently back-transformed to the atomistic level using a resolution-transformation protocol. The configurations sampled at the CG level are stable in the atomistic simulation. The effect of helicity on pore stability is investigated at the CG level and we find that partial helicity is required to form stable pores. We also show that the current CG scheme can be used to study spontaneous poration by magainin-H2 peptides. Overall, our simulations provide a multi-scale view of a fundamental biophysical membrane process involving a complex interplay between peptides and lipids.
- Published
- 2010
209. Location, Tilt, and Binding
- Author
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Marlon J. Hinner, Siewert J. Marrink, Alex H. de Vries, and Molecular Dynamics
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Force field (chemistry) ,COMPUTER-SIMULATION ,VESICLES ,Molecular dynamics ,Membrane Lipids ,PERMEATION ,Computational chemistry ,COARSE-GRAINED MODEL ,Amphiphile ,FLIP-FLOP ,Materials Chemistry ,Molecule ,Computer Simulation ,Physical and Theoretical Chemistry ,FLUORESCENCE ,Lipid bilayer ,Fluorescent Dyes ,Binding Sites ,Chemistry ,Vesicle ,LIPID-MEMBRANES ,FREE-ENERGY ,ANELLATED HEMICYANINE DYES ,Surfaces, Coatings and Films ,Membrane ,Models, Chemical ,Chemical physics ,FORCE-FIELD ,Thermodynamics ,Umbrella sampling - Abstract
We present a molecular dynamics study on the interaction of styryl-type voltage-sensitive dyes with a lipid membrane. In this work, voltage-sensitive dyes are proposed as interesting model amphiphiles for biomolecular simulation, due to the wealth of biophysical and thermodynamical data available on their behavior and their binding to lipid membranes. Taking this data as a basis, we tested the recently developed MARTINI coarse-grained model (J. Phys. Chem. B 2007, 111, 7812). The focus was on the fast computation of the free energy of membrane binding. As a first step, we investigated the tilt and location of a coarse-grained representation of the dye Di-4-ASPBS in a lipid membrane, and found good agreement with atomistic simulations and experimental data. Then, we performed umbrella sampling to obtain the theoretical binding free energy for a number of Di-4-ASPBS derivates. In most cases, simulation and experimental binding data were in good agreement regarding the impact of structural changes in the amphiphile on binding. The work yields a general molecular picture of how such structural variations lead to changes of the binding mode and binding strength of amphiphiles to lipid membranes. Further, it provides insights into the possibilities and current limitations of rapid free energy computation for membrane binding with the coarse-grained MARTINI model. The results suggest that the MARTINI model may be a generally useful tool for the study and optimization of molecules interacting with membranes, such as biophysical probes or pharmaceutical compounds.
- Published
- 2009
210. Martini Coarse-Grained Force Field
- Author
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Alex H. de Vries, Andrzej J. Rzepiela, Lubbert Dijkhuizen, Philippe H. Hünenberger, Cesar A. Lopez, Siewert J. Marrink, Groningen Biomolecular Sciences and Biotechnology, Zernike Institute for Advanced Materials, and Molecular Dynamics
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chemistry.chemical_classification ,Kojibiose ,MOLECULAR-DYNAMICS SIMULATIONS ,Sophorose ,Nigerose ,HELICAL STRUCTURE ,Glycosidic bond ,Cellobiose ,Curdlan ,Maltose ,FREE-ENERGY ,V-AMYLOSE ,AQUEOUS-SOLUTION ,Computer Science Applications ,chemistry.chemical_compound ,Crystallography ,CONFORMATIONAL BEHAVIOR ,chemistry ,Chemical physics ,PACKING ANALYSIS ,ATOMIC-RESOLUTION ,Monosaccharide ,SINGLE-CRYSTALS ,PHOSPHOLIPID-BILAYER ,Physical and Theoretical Chemistry - Abstract
We present an extension of the Martini coarse-grained force field to carbohydrates. The parametrization follows the same philosophy as was used previously for lipids and proteins, focusing on the reproduction of partitioning free energies of small compounds between polar and nonpolar phases. The carbohydrate building blocks considered are the monosaccharides glucose and fructose and the disaccharides sucrose, trehalose, maltose, cellobiose, nigerose, laminarabiose, kojibiose, and sophorose. Bonded parameters for these saccharides are optimized by comparison to conformations sampled with an atomistic force field, in particular with respect to the representation of the most populated rotameric state for the glycosidic bond. Application of the new coarse-grained carbohydrate model to the oligosaccharides amylose and Curdlan shows a preservation of the main structural properties with 3 orders of magnitude more efficient sampling than the atomistic counterpart. Finally, we investigate the cryo- and anhydro-protective effect of glucose and trehalose on a lipid bilayer and find a strong decrease of the melting temperature, in good agreement with both experimental findings and atomistic simulation studies.
- Published
- 2009
211. Stability of Asymmetric Lipid Bilayers Assessed by Molecular Dynamics Simulations
- Author
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Siewert J. Marrink, Santi Esteban-Martín, H. Jelger Risselada, Jesús Salgado, Groningen Biomolecular Sciences and Biotechnology, Zernike Institute for Advanced Materials, and Molecular Dynamics
- Subjects
1,2-Dipalmitoylphosphatidylcholine ,Lipid Bilayers ,Biochemistry ,Catalysis ,Colloid and Surface Chemistry ,COARSE-GRAINED MODEL ,SHAPE TRANSFORMATIONS ,Monolayer ,Computer Simulation ,Lipid bilayer phase behavior ,Lipid bilayer ,Chemistry ,Bilayer ,Lipid bilayer fusion ,Biological membrane ,General Chemistry ,Lipid bilayer mechanics ,ANTIMICROBIAL PEPTIDES ,Crystallography ,Membrane ,TRANSMEMBRANE DISTRIBUTION ,EGG PHOSPHATIDYLCHOLINE ,Phosphatidylcholines ,PORE FORMATION ,Biophysics ,PRESSURE PROFILES ,MECHANOSENSITIVE CHANNEL ,lipids (amino acids, peptides, and proteins) ,OCTYL GLUCOSIDE ,PHOSPHOLIPID-BILAYERS - Abstract
The asymmetric insertion of amphiphiles into biological membranes compromises the balance between the inner and outer monolayers. As a result, area expansion of the receiving leaflet and curvature strain may lead to membrane permeation, shape changes, or membrane fusion events. We have conducted both atomistic and coarse-grained molecular dynamics simulations of dipalmitoyl-phosphatidylcholine (DPPC) bilayers to study the effect of an asymmetric distribution of lipids between the two monolayers on membrane stability. Highly asymmetric lipid bilayers were found to be surprisingly stable within the submicrosecond time span of the simulations. Even the limiting case of a monolayer immersed in water ruptured spontaneously only after at least 20 ns simulation. A thermal shock could destabilize these kinetically trapped states. We also studied mixed systems composed of DPPC and short tail diC(8)PC lipids, showing that the presence of the cone-shaped short tail lipid facilitates the release of tension in the asymmetric systems via formation of a transmembrane pore. Thus, asymmetric area expansion and curvature stress cooperate to yield bilayer disruption. It appears that, although asymmetric area expansion destabilizes the bilayer structure, the activation energy for transmonolayer lipid re-equilibration is increased. Such a large kinetic barrier can be reduced by lipids with positive spontaneous curvature. These effects are important at the onset of bilayer destabilization phenomena, such as lipid pore formation and membrane fusion, and should be considered for the mechanism of induction of such processes by peptides and proteins.
- Published
- 2009
212. Lipids on the move: Simulations of membrane pores, domains, stalks and curves
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D. Peter Tieleman, Siewert J. Marrink, and Alex H. de Vries
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Models, Molecular ,SELF-ASSEMBLED MEMBRANES ,MOLECULAR-DYNAMICS SIMULATIONS ,Vesicle fusion ,Membrane Fluidity ,Biophysics ,VESICLE FUSION ,Nanotechnology ,Molecular dynamics ,010402 general chemistry ,Models, Biological ,01 natural sciences ,Biochemistry ,Membrane Lipids ,Membrane Microdomains ,Non-lamellar phase ,Membrane pore ,VOLTAGE SENSOR ,COARSE-GRAINED MODEL ,0103 physical sciences ,Animals ,Humans ,Computer Simulation ,IONIC CHARGE IMBALANCE ,COMPUTER-SIMULATIONS ,010304 chemical physics ,Chemistry ,Computer modeling ,Vesicle ,ARGININE SIDE-CHAIN ,Dissipative particle dynamics ,Biological membrane ,Self-assembly ,Cell Biology ,Phase transformation ,ANTIMICROBIAL PEPTIDES ,Cellular Structures ,0104 chemical sciences ,Membrane ,Lipid flip-flop ,DISSIPATIVE PARTICLE DYNAMICS ,lipids (amino acids, peptides, and proteins) ,Energy Metabolism ,Membrane biophysics - Abstract
In this review we describe the state-of-the-art of computer simulation studies of lipid membranes. We focus on collective lipid-lipid and lipid-protein interactions that trigger deformations of the natural lamellar membrane state, showing that many important biological processes including self-aggregation of membrane components into domains, the formation of non-lamellar phases, and membrane poration and curving, are now amenable to detailed simulation studies. (C) 2008 Elsevier B.V. All rights reserved.
- Published
- 2009
213. The freezing process of small lipid vesicles at molecular resolution
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H. Jelger Risselada, Siewert J. Marrink, and Molecular Dynamics
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Liposome ,Membrane permeability ,Bilayer ,Vesicle ,BILAYER VESICLES ,General Chemistry ,Condensed Matter Physics ,DYNAMICS SIMULATION ,MEMBRANES ,DETAIL ,Crystallography ,chemistry.chemical_compound ,Membrane ,FUSION ,chemistry ,COARSE-GRAINED MODEL ,Dipalmitoylphosphatidylcholine ,Phase (matter) ,PHOSPHOLIPID-VESICLES ,Biophysics ,WATER ,Lamellar structure ,GEL PHASE ,TRANSITION - Abstract
At present very little is known about the kinetic barriers which a small vesicle will face during the transformation from the liquid-crystalline to the gel phase, and what the structure of frozen vesicles looks like at the molecular level. The formation of gel domains in the strongly curved bilayer of a small vesicle seems almost paradoxical and is expected to involve large structural reorganizations. In this work we use coarse-grained molecular dynamics simulations to study the kinetic and structural aspects of gel domain formation in small lipid vesicles, specifically dipalmitoylphosphatidylcholine (DPPC) vesicles with a diameter range of 20-40 nm. We observe that cooling of such vesicles below the phase transition temperature does not result in gel phase formation on a microsecond time scale, which we attribute to the presence of an effective area constraint. This area constraint is due to the strongly reduced membrane permeability at lower temperatures, preventing the rapid efflux of water and the required decrease in membrane area to form a gel phase. Control simulations with lamellar bilayers, simulated at fixed area, show that gel phase formation is indeed only possible below a certain threshold area. The effect of lipid asymmetry was also studied with the lamellar setup, and found to be of less importance. To circumvent the kinetic barrier imposed by the effective area constraint of the liposomes, i.e. to mimic the long time behavior, we introduce artificial pores in the membrane facilitating the solvent efflux. In this case, spontaneous gel domains are formed. We identify several stages during the microsecond-long transformation, finally resulting in strongly deformed or ruptured vesicles entirely in the gel state.
- Published
- 2009
214. The molecular face of lipid rafts in model membranes
- Author
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Siewert J. Marrink, H. Jelger Risselada, Groningen Biomolecular Sciences and Biotechnology, Zernike Institute for Advanced Materials, Molecular Dynamics, and Faculty of Science and Engineering
- Subjects
Models, Molecular ,polyunsaturated ,VESICLES ,Cell membrane ,Molecular dynamics ,Membrane Microdomains ,COARSE-GRAINED MODEL ,Phase (matter) ,Monolayer ,coarse-grained ,medicine ,Computer Simulation ,FIELD ,Lipid raft ,Multidisciplinary ,DOMAIN FORMATION ,Chemistry ,Vesicle ,CHOLESTEROL ,FLUORESCENCE MICROSCOPY ,liquid-ordered ,PHASE-FORMATION ,Raft ,Biological Sciences ,molecular dynamics ,NMR ,Crystallography ,Membrane ,medicine.anatomical_structure ,Chemical physics ,SIMULATION ,MIXED BILAYERS - Abstract
Cell membranes contain a large number of different lipid species. Such a multicomponent mixture exhibits a complex phase behavior with regions of structural and compositional heterogeneity. Especially domains formed in ternary mixtures, composed of saturated and unsaturated lipids together with cholesterol, have received a lot of attention as they may resemble raft formation in real cells. Here we apply a simulation model to assess the molecular nature of these domains at the nanoscale, information that has thus far eluded experimental determination. We are able to show the spontaneous separation of a saturated phosphatidylcholine (PC)/unsaturated PC/cholesterol mixture into a liquid-ordered and a liquid-disordered phase with structural and dynamic properties closely matching experimental data. The near-atomic resolution of the simulations reveals remarkable features of both domains and the boundary domain interface. Furthermore, we predict the existence of a small surface tension between the monolayer leaflets that drives registration of the domains. At the level of molecular detail, raft-like lipid mixtures show a surprising face with possible implications for many cell membrane processes.
- Published
- 2008
215. Application of mean field boundary potentials in simulations of lipid vesicles
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Alan E. Mark, H. Jelger Risselada, Siewert J. Marrink, Molecular Dynamics, and Zernike Institute for Advanced Materials
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BILAYERS ,MOLECULAR-DYNAMICS SIMULATIONS ,1,2-Dipalmitoylphosphatidylcholine ,Lipid Bilayers ,Boundary (topology) ,MEMBRANES ,DETAIL ,FUSION ,COARSE-GRAINED MODEL ,Materials Chemistry ,WATER ,Computer Simulation ,Physical and Theoretical Chemistry ,COMPUTER-SIMULATIONS ,Fusion ,Range (particle radiation) ,Chemistry ,Vesicle ,Nanosecond ,Surfaces, Coatings and Films ,Solvent ,Crystallography ,Membrane ,Mean field theory ,Chemical physics ,Liposomes - Abstract
A method is presented to enhance the efficiency of simulations of lipid vesicles. The method increases computational speed by eliminating water molecules that either surround the vesicle or reside in the interior of the vesicle, without altering the properties of the water at the membrane interface. Specifically, mean field force approximation (MFFA) boundary potentials are used to replace both the internal and external excess bulk solvent. In addition to reducing the cost of simulating preformed vesicles, the molding effect of the boundary potentials also enhances the formation and equilibration of vesicles from random solutions of lipid in water. Vesicles with diameters in the range from 20 to 60 nm were obtained on a nanosecond time scale, without any noticeable effect of the boundary potentials on their structure.
- Published
- 2008
216. Mechanosensitive membrane channels in action
- Author
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Siewert J. Marrink, S. Yefimov, Erik Van der Giessen, Patrick Onck, and Zernike Institute for Advanced Materials
- Subjects
Models, Molecular ,MOLECULAR-DYNAMICS SIMULATIONS ,Mutant ,Lipid Bilayers ,Biophysics ,ION-CHANNEL ,Gating ,Biophysical Theory and Modeling ,Mechanotransduction, Cellular ,Models, Biological ,Ion Channels ,Cell membrane ,STRUCTURAL MODELS ,Molecular dynamics ,COARSE-GRAINED MODEL ,medicine ,GATING MECHANISM ,Computer Simulation ,Lipid bilayer ,Ion channel ,Chemistry ,Escherichia coli Proteins ,Cell Membrane ,Crystallography ,medicine.anatomical_structure ,Models, Chemical ,SMALL PHOSPHOLIPID-VESICLES ,ESCHERICHIA-COLI ,LARGE-CONDUCTANCE ,Membrane channel ,Mechanosensitive channels ,Stress, Mechanical ,MYCOBACTERIUM-TUBERCULOSIS ,Ion Channel Gating ,Mechanoreceptors ,LIPID-COMPOSITION - Abstract
The tension-driven gating process of MscL from Mycobacterium tuberculosis, Tb-MscL, has been addressed at near-atomic detail using coarse-grained molecular dynamics simulations. To perform the simulations, a novel coarse-grained peptide model based on a thermodynamic parameterization of the amino-acid side chains has been applied. Both the wild-type Tb-MscL and its gain-of-function mutant V21 D embedded in a solvated lipid bilayer have been studied. To mimic hypoosmotic shock conditions, simulations were performed at increasing levels of membrane tension approaching the rupture threshold of the lipid bilayer. Both the wild-type and the mutant channel are found to undergo significant conformational changes in accordance with an irislike expansion mechanism, reaching a conducting state on a microsecond timescale. The most pronounced expansion of the pore has been observed for the V21 D mutant, which is consistent with the experimentally shown gain-of-function phenotype of the V21 D mutant.
- Published
- 2008
217. Structure of spheroidal HDL particles revealed by combined atomistic and coarse-grained simulations
- Author
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Martin K. Jones, Denys Bashtovyy, Siewert J. Marrink, James C. Patterson, Andrea Catte, Ling Li, Perttu S. Niemelä, Ilpo Vattulainen, Feifei Gu, Aldo Rampioni, Mikko Karttunen, Durba Sengupta, Jere P. Segrest, Timo Vuorela, Groningen Biomolecular Sciences and Biotechnology, Molecular Dynamics, and Faculty of Science and Engineering
- Subjects
MOLECULAR-DYNAMICS SIMULATIONS ,BELT MODEL ,Surface Properties ,Lipid Bilayers ,Biophysics ,Molecular Conformation ,Supramolecular Assemblies ,010402 general chemistry ,01 natural sciences ,Models, Biological ,LIPID-BOUND CONFORMATION ,03 medical and health sciences ,chemistry.chemical_compound ,Molecular dynamics ,High-density lipoprotein ,Phospholipid transfer protein ,polycyclic compounds ,Moiety ,Organic chemistry ,Molecule ,Animals ,Humans ,Computer Simulation ,Lipid bilayer ,030304 developmental biology ,0303 health sciences ,Apolipoprotein A-I ,APOLIPOPROTEIN-A-I ,LECITHIN-CHOLESTEROL ACYLTRANSFERASE ,nutritional and metabolic diseases ,MASS-SPECTROMETRY ,0104 chemical sciences ,Protein Structure, Tertiary ,Cholesterol ,chemistry ,Liver ,CARDIOVASCULAR-DISEASE ,Cholesteryl ester ,Phosphatidylcholines ,Solvents ,FORCE-FIELD ,lipids (amino acids, peptides, and proteins) ,PHOSPHOLIPID TRANSFER PROTEIN ,Lipoproteins, HDL ,HIGH-DENSITY-LIPOPROTEIN ,Lipoprotein - Abstract
Spheroidal high-density lipoprotein (HDL) particles circulating in the blood are formed through an enzymatic process activated by apoA-I, leading to the esterification of cholesterol, which creates a hydrophobic core of cholesteryl ester molecules in the middle of the discoidal phospholipid bilayer. In this study, we investigated the conformation of apoA-I in model spheroidal HDL (ms-HDL) particles using both atomistic and coarse-grained molecular dynamics simulations, which are found to provide consistent results for all HDL properties we studied. The observed small contribution of cholesteryl oleate molecules to the solvent-accessible surface area of the entire ms-HDL particle indicates that palmitoyloleoylphosphatidylcholines and apoA-I molecules cover the hydrophobic core comprised of cholesteryl esters particularly well. The ms-HDL particles are found to form a prolate ellipsoidal shape, with sizes consistent with experimental results. Large rigid domains and low mobility of the protein are seen in all the simulations. Additionally, the average number of contacts of cholesteryl ester molecules with apoA-I residues indicates that cholesteryl esters interact with protein residues mainly through their cholesterol moiety. We propose that the interaction of annular cholesteryl oleate molecules contributes to apoA-I rigidity stabilizing and regulating the structure and function of the ms-HDL particle.
- Published
- 2008
218. Electrophoretic mobility does not always reflect the charge on an oil droplet
- Author
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Herre Jelger Risselada, Volker Knecht, Alan E. Mark, Siewert J. Marrink, Groningen Biomolecular Sciences and Biotechnology, Zernike Institute for Advanced Materials, and Molecular Dynamics
- Subjects
IONS ,MOLECULAR-DYNAMICS SIMULATIONS ,Hydronium ,SURFACE ,Surface Properties ,Static Electricity ,electrokinetic phenomena ,Analytical chemistry ,POTENTIALS ,LIQUID-VAPOR INTERFACE ,Heptanes ,Biomaterials ,Physics::Fluid Dynamics ,chemistry.chemical_compound ,zeta potential ,water structure ,Colloid and Surface Chemistry ,SYSTEMS ,DEFORMATION ,Electric field ,AQUEOUS-SOLUTIONS ,Zeta potential ,computer simulation ,WATER ,Surface charge ,Point of zero charge ,Chemistry ,molecular dynamics ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,Electrophoresis ,Isoelectric point ,Models, Chemical ,Chemical physics ,Oil droplet ,electrophoresis ,Adsorption ,HYDROCARBONS ,Hydrophobic and Hydrophilic Interactions ,Oils - Abstract
Electrophoresis is widely used to determine the electrostatic potential of colloidal particles. Oil droplets in pure water show negative or positive electrophoretic mobilities depending on the pH. This is commonly attributed to the adsorption of hydroxyl or hydronium ions, resulting in a negative or positive surface charge, respectively. This explanation, however, is not in agreement with the difference in isoelectric point and point of zero charge observed in experiment. Here we present molecular dynamics simulations of oil droplets in water in the presence of an external electric field but in the absence of any ions. The simulations reproduce the negative sign and the order of magnitude of the oil droplet mobilities at the point of zero charge in experiment. The electrostatic potential in the oil with respect to the water phase, induced by anisotropic dipole orientation in the interface, is positive. Our results suggest that electrophoretic mobility does not always reflect the net charge or electrostatic potential of a suspended liquid droplet and, thus, the interpretation of electrophoresis in terms of purely continuum effects may need to be reevaluated. (C) 2007 Elsevier Inc. All rights reserved.
- Published
- 2008
219. Pressure-area isotherm of a lipid monolayer from molecular dynamics simulations
- Author
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D. Peter Tieleman, Siewert J. Marrink, Luca Monticelli, Svetlana Baoukina, Groningen Biomolecular Sciences and Biotechnology, and Molecular Dynamics
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LANGMUIR MONOLAYERS ,Equation of state ,BILAYERS ,1,2-Dipalmitoylphosphatidylcholine ,Molecular model ,Thermodynamics ,AIR/WATER INTERFACE ,02 engineering and technology ,010402 general chemistry ,Plateau (mathematics) ,01 natural sciences ,COEXISTENCE ,Molecular dynamics ,Condensed Matter::Materials Science ,COARSE-GRAINED MODEL ,Phase (matter) ,Monolayer ,Pressure ,Electrochemistry ,Computer Simulation ,General Materials Science ,Spectroscopy ,DOMAIN FORMATION ,Chemistry ,technology, industry, and agriculture ,Membranes, Artificial ,PHASE-FORMATION ,UNDULATIONS ,Surfaces and Interfaces ,Lipid monolayer ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,EQUATION-OF-STATE ,0104 chemical sciences ,PHOSPHATIDYLCHOLINE MONOLAYERS ,Condensed Matter::Soft Condensed Matter ,Models, Chemical ,High pressure ,Physical chemistry ,0210 nano-technology - Abstract
We calculated the pressure-area isotherm of a dipalmitoyl-phosphatidylcholine (DPPC) lipid monolayer from molecular dynamics simulations using a coarse-grained molecular model. We characterized the monolayer structure, geometry, and phases directly from the simulations and compared the calculated isotherm to experiments. The calculated isotherm shows liquid-expanded and liquid-condensed phases and their coexistence plateau. At high pressure, the monolayer surface is rippled; upon further compression, the monolayer undergoes a collapse. We studied the effect of temperature and system size on the isotherm slope and phase coexistence region. Thermodynamic and dynamic properties of the monolayer phases were also investigated.
- Published
- 2007
220. Comparison of Thermodynamic Properties of Coarse-Grained and Atomic-Level Simulation Models
- Author
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Riccardo Baron, Daniel Trzesniak, Andreas Elsener, Alex H. de Vries, Siewert J. Marrink, Wilfred F. van Gunsteren, Moleculaire Dynamica, Faculty of Science and Engineering, Theoretische Chemie, and Groningen Biomolecular Sciences and Biotechnology
- Subjects
Chemical Phenomena ,GROMACS ,Thermodynamics ,Ion ,GROMOS ,Entropy (classical thermodynamics) ,Molecular dynamics ,Alkanes ,Vaporization ,Computer Simulation ,Physical and Theoretical Chemistry ,energy–entropy compensation ,Chemistry, Physical ,Chemistry ,force field ,Simulation modeling ,Solvation ,Water ,Atmospheric temperature range ,computational chemistry ,Atomic and Molecular Physics, and Optics ,Models, Chemical ,Solvents ,Material properties ,Oils - Abstract
Thermodynamic data are often used to calibrate or test atomic-level (AL) force fields for molecular dynamics (MD) simulations. In contrast, the majority of coarse-grained (CG) force fields do not rely extensively on thermodynamic quantities. Recently, a CG force field for lipids, hydrocarbons, ions, and water, [1] in which approximately four non-hydrogen atoms are mapped onto one interaction site, has been proposed and applied to study various aspects of lipid systems. To date, no extensive investigation of its capability to describe salvation thermodynamics has been undertaken. In the present study, a detailed picture of vaporization, solvation, and phase-partitioning thermodynamics for liquid hydrocarbons and water was obtained at CG and AL resolutions, in order to compare the two types of models and evaluate their ability to describe thermodynamic properties in the temperature range between 263 and 343 K. Both CG and AL models capture the experimental dependence of the thermodynamic properties on the temperature, albeit a systematically weaker dependence is found for the CG model. Moreover, deviations are found for solvation thermodynamics and for the corresponding enthalpy-entropy compensation for the CG model. Particularly water/oil repulsion seems to be overestimated. However, the results suggest that the thermodynamic properties considered should be reproducible by a CG model provided it is reparametrized on the basis of these liquid-phase properties.
- Published
- 2007
221. Does isoprene protect plant membranes for thermal shock? A molecular dynamics study
- Author
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Anton J.M. Schoot Uiterkamp, Alex H. de Vries, Arkadiusz Kozubek, Alan E. Mark, Siewert J. Marrink, M.E. Siwko, Faculty of Science and Engineering, and Molecular Dynamics
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0106 biological sciences ,Models, Molecular ,Thermotolerance ,Work (thermodynamics) ,Molecular dynamic ,Hot Temperature ,Isoprene ,Lipid Bilayers ,Phospholipid ,Biophysics ,01 natural sciences ,Biochemistry ,03 medical and health sciences ,chemistry.chemical_compound ,Molecular dynamics ,Membrane Lipids ,Hemiterpenes ,Pentanes ,Mole ,Butadienes ,Molecule ,Organic chemistry ,Computer Simulation ,Lipid bilayer ,Phospholipids ,030304 developmental biology ,0303 health sciences ,Cell Membrane ,Temperature ,Membrane ,Cell Biology ,Plant ,Plants ,chemistry ,Dimyristoylphosphatidylcholine ,Simulation ,010606 plant biology & botany - Abstract
The question of why plants release isoprene when heat stressed has been continuously debated for more than half a century. In this work we use molecular dynamics simulation techniques to directly investigate the interaction between isoprene and a model phospholipid membrane in atomic detail. It is found that isoprene partitions preferentially in the center of the membrane and in a dose dependent manner enhances the order within the membrane without significantly changing the dynamical properties of the system. At a concentration of 20 mol% isoprene (16 isoprene molecules per 64 lipid molecules) the effect of the addition of isoprene on the membrane order is equivalent to a reduction in temperature of 10 K, rising to a reduction of 30 K at 43 mol% isoprene. The significance of the work is that it provides for the first time direct evidence that isoprene stabilizes lipid membranes and reduces the likelihood of a phospholipid membrane undergoing a heat induced phase transition. Furthermore it provides a clear mechanistic picture as to why plants specifically utilize isoprene for this purpose.
- Published
- 2007
222. From light-harvesting to photoprotection
- Author
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Roberta Croce, Xavier Periole, Nicoletta Liguori, Siewert J. Marrink, Biophysics Photosynthesis/Energy, LaserLaB - Energy, Molecular Dynamics, and Electron Microscopy
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Models, Molecular ,chemistry.chemical_classification ,Quenching ,Multidisciplinary ,Light ,Light-Harvesting Protein Complexes ,Biology ,Article ,Microsecond ,chemistry.chemical_compound ,Molecular dynamics ,chemistry ,Neoxanthin ,Xanthophyll ,Photoprotection ,Botany ,Biophysics ,SDG 7 - Affordable and Clean Energy ,Antenna (radio) ,Plant Physiological Phenomena ,Excitation - Abstract
Light-Harvesting Complex II (LHCII) is largely responsible for light absorption and excitation energy transfer in plants in light-limiting conditions, while in high-light it participates in photoprotection. It is generally believed that LHCII can change its function by switching between different conformations. However, the underlying molecular picture has not been elucidated yet. The available crystal structures represent the quenched form of the complex, while solubilized LHCII has the properties of the unquenched state. To determine the structural changes involved in the switch and to identify potential quenching sites, we have explored the structural dynamics of LHCII, by performing a series of microsecond Molecular Dynamics simulations. We show that LHCII in the membrane differs substantially from the crystal and has the signatures that were experimentally associated with the light-harvesting state. Local conformational changes at the N-terminus and at the xanthophyll neoxanthin are found to strongly correlate with changes in the interactions energies of two putative quenching sites. In particular conformational disorder is observed at the terminal emitter resulting in large variations of the excitonic coupling strength of this chlorophyll pair. Our results strongly support the hypothesis that light-harvesting regulation in LHCII is coupled with structural changes.
- Published
- 2015
223. Adaptive resolution simulation of polarizable supramolecular coarse-grained water models
- Author
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Julija Zavadlav, Siewert J. Marrink, Matej Praprotnik, Manuel N. Melo, and Molecular Dynamics
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Models, Molecular ,DYNAMICS ,Chemistry ,Point particle ,Static Electricity ,Molecular Conformation ,Solvation ,Water ,General Physics and Astronomy ,SOFT MATTER ,Force field (chemistry) ,Dipole ,Classical mechanics ,Polarizability ,BIOMOLECULAR SIMULATIONS ,SYSTEMS ,Electric field ,MULTISCALE SIMULATION ,Solvents ,Water model ,FORCE-FIELD ,Statistical physics ,Soft matter ,Physical and Theoretical Chemistry ,COMPUTER-SIMULATIONS - Abstract
Multiscale simulations methods, such as adaptive resolution scheme, are becoming increasingly popular due to their significant computational advantages with respect to conventional atomistic simulations. For these kind of simulations, it is essential to develop accurate multiscale water models that can be used to solvate biophysical systems of interest. Recently, a 4-to-1 mapping was used to couple the bundled-simple point charge water with the MARTINI model. Here, we extend the supramolecular mapping to coarse-grained models with explicit charges. In particular, the two tested models are the polarizable water and big multiple water models associated with the MARTINI force field. As corresponding coarse-grained representations consist of several interaction sites, we couple orientational degrees of freedom of the atomistic and coarse-grained representations via a harmonic energy penalty term. This additional energy term aligns the dipole moments of both representations. We test this coupling by studying the system under applied static external electric field. We show that our approach leads to the correct reproduction of the relevant structural and dynamical properties. (C) 2015 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 Unported License.
- Published
- 2015
224. MARTINI Coarse-Grained Model for Crystalline Cellulose Microfibers
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Paul Langan, Siewert J. Marrink, Shishir P. S. Chundawat, Cesar A. Lopez, Giovanni Bellesia, Sandrasegaram Gnanakaran, Bruce E. Dale, Antonio Redondo, and Molecular Dynamics
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Length scale ,Models, Molecular ,INTERCONVERSION ,business.product_category ,Materials science ,Nanotechnology ,Cellobiose ,PRETREATMENT ,LIGNOCELLULOSIC BIOMASS ,chemistry.chemical_compound ,Microfiber ,Materials Chemistry ,Carbohydrate Conformation ,Physical and Theoretical Chemistry ,Cellulose ,Carbohydrate composition ,Elastic modulus ,NATIVE CELLULOSE ,Mechanical Phenomena ,ELASTIC-MODULUS ,SPECTROSCOPY ,Polymer science ,Temperature ,TRANSFORMATION ,Surfaces, Coatings and Films ,Cellulose fiber ,chemistry ,Nanofiber ,X-RAY ,FORCE-FIELD ,Thermodynamics ,business ,I-BETA - Abstract
Commercial-scale biofuel production requires a deep understanding of the structure and dynamics of its principal target: cellulose. However, an accurate description and modeling of this carbohydrate structure at the mesoscale remains elusive, particularly because of its overwhelming length scale and configurational complexity. We have derived a set of MARTINI coarse-grained force field parameters for the simulation of crystalline cellulose fibers. The model is adapted to reproduce different physicochemical and mechanical properties of native cellulose I beta. The model is able not only to handle a transition from cellulose I beta to another cellulose allomorph, cellulose IIII, but also to capture the physical response to temperature and mechanical bending of longer cellulose nanofibers. By developing the MARTINI model of a solid cellulose crystalline fiber from the building blocks of a soluble cellobiose coarse-grained model, we have provided a systematic way to build MARTINI models for other crystalline biopolymers.
- Published
- 2015
225. Computational Lipidomics and the Lipid Organization of Cell Envelopes
- Author
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Siewert J. Marrink, Manuel N. Melo, D. Peter Tieleman, Helgi I. Ingólfsson, Tsjerk A. Wassenaar, Alex H. de Vries, Xavier Periole, and Molecular Dynamics
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0303 health sciences ,Bilayer ,Cell ,Biophysics ,Nanotechnology ,Lipidome ,Biology ,Domain formation ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,Membrane ,Membrane protein ,Lipidomics ,ComputingMethodologies_DOCUMENTANDTEXTPROCESSING ,medicine ,lipids (amino acids, peptides, and proteins) ,GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries) ,Membrane biophysics ,030217 neurology & neurosurgery ,030304 developmental biology - Abstract
The detailed lipid organization of cellular membranes remains elusive. A typical plasma membrane contains hundreds of different lipid species that are actively regulated by the cell. Currently over 30,000 biologically relevant lipids have been identified and specific organisms often synthesize thousands of different lipid types. This is far greater diversity than is needed to maintain bilayer barrier properties and to solvate membrane proteins. Why organisms go through the costly progress of creating and maintaining such a large diversity of lipids is one of the big open questions in biology. What is the individual role of these lipids, and how do they interact and organize in the membrane plane?To start to address these questions we optimized and developed the Martini coarse-grained force field lipidome. We systematically explore over a hundred different lipid types using the Martini model. Bulk properties of each individual lipid type (e.g. bilayer thickness, area per lipid, diffusion, order parameter and area compressibility) were analyzed and overall trends compared to experimental values. Using pre-existing Martini lipids and the newly characterized ones, idealized plasma membranes containing dozens of different lipid types asymmetrically distributed between the membrane leaflets were constructed and simulated on the multi microsecond time scale. In terms of lipid composition these are by an order of magnitude the most complex simulations to date. These large-scale simulations provide a high-resolution view on the lipid organization of plasma membranes at an unprecedented level of complexity and allow us to analyze a variety of plasma membrane physicochemical properties, including: lipid-lipid interactions, bilayer bulk material properties, domain formation and coupling between the bilayer leaflets. Overall, the plasma membranes show global non-ideal mixing of different lipid species at different spatiotemporal scales.
- Published
- 2015
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226. Intramolecular photostabilization via triplet-state quenching: design principles to make organic fluorophores 'self-healing'
- Author
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Siewert J. Marrink, Lourens-Jan Ugen, Thorben Cordes, Jaakko J. Uusitalo, Jasper H. M. van der Velde, Eliza M. Warszawik, Andreas Herrmann, Molecular Biophysics, Molecular Dynamics, Polymer Chemistry and Bioengineering, and Nanotechnology and Biophysics in Medicine (NANOBIOMED)
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DYNAMICS ,MECHANISM ,Fluorophore ,MOLECULE FLUORESCENCE SPECTROSCOPY ,Design elements and principles ,Nanotechnology ,Molecular Dynamics Simulation ,Photochemistry ,chemistry.chemical_compound ,Molecular dynamics ,Physical and Theoretical Chemistry ,Triplet state ,OXIDIZING SYSTEM ,Quenching (fluorescence) ,HYDRATION ,MICROSCOPY ,Carbocyanines ,Photochemical Processes ,CYANINE FLUOROPHORES ,LASER-DYES ,chemistry ,Microscopy, Fluorescence ,Covalent bond ,Intramolecular force ,Self-healing ,ENERGY-TRANSFER ,PHOTOPHYSICS - Abstract
Covalent linkage of fluorophores and photostabilizers was recently revived as a strategy to make organic fluorophores “self-healing” via triplet-state quenching. Although Lüttke and co-workers pioneered this strategy already in the 1980s, the general design principles still remain elusive. In this contribution, we combine experiments and theory to understand what determines the photostabilization efficiency in dye–photostabilizer conjugates. Our results from single-molecule microscopy and molecular dynamics simulations of different Cy5-derivatives suggest that the distance and relative geometry between the fluorophore and photostabilizer are more important than the chemical nature of the photostabilizer, e.g. its redox potential, which is known to influence electron-transfer rates. We hypothesize that the efficiency of photostabilization scales directly with the contact rate of the fluorophore and photostabilizer. This study represents an important step in the understanding of the molecular mechanism of intramolecular photostabilization and can pave the way for further development of stable emitters for various applications.
- Published
- 2015
227. Antimicrobial Peptides in Action
- Author
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and Alan E. Mark, Hari Leontiadou, Siewert J. Marrink, Groningen Biomolecular Sciences and Biotechnology, Molecular Dynamics, and Faculty of Science and Engineering
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Models, Molecular ,Cell Membrane Permeability ,MOLECULAR-DYNAMICS SIMULATIONS ,1,2-Dipalmitoylphosphatidylcholine ,Stereochemistry ,Lipid Bilayers ,Molecular Sequence Data ,Antimicrobial peptides ,INSERTION ,Phospholipid ,Peptide ,Models, Biological ,Biochemistry ,Catalysis ,chemistry.chemical_compound ,Colloid and Surface Chemistry ,ANALOG ,Computer Simulation ,Amino Acid Sequence ,LIPID-BILAYERS ,Lipid bilayer ,Peptide sequence ,chemistry.chemical_classification ,Bilayer ,Magainin ,Water ,AMPHIPATHIC PEPTIDES ,General Chemistry ,Lipid Metabolism ,Lipids ,Membrane ,chemistry ,PORE FORMATION ,Biophysics ,MEMBRANE ,ORIENTATION ,PHOSPHOLIPID-BILAYERS ,MAGAININ ,Antimicrobial Cationic Peptides - Abstract
Molecular dynamics simulations of the magainin MG-H2 peptide interacting with a model phospholipid membrane have been used to investigate the mechanism by which antimicrobial peptides act. Multiple copies of the peptide were randomly placed in solution close to the membrane. The peptide readily bound to the membrane, and above a certain concentration, the peptide was observed to cooperatively induce the formation of a nanometer- sized, toroidally shaped pore in the bilayer. In sharp contrast with the commonly accepted model of a toroidal pore, only one peptide was typically found near the center of the pore. The remaining peptides lay close to the edge of the pore, maintaining a predominantly parallel orientation with respect to the membrane.
- Published
- 2006
228. Ironing out their differences: dissecting the structural determinants of a phenylalanine aminomutase and ammonia lyase
- Author
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Dick B. Janssen, Marcelo F. Masman, Sebastian Bartsch, Bauke W. Dijkstra, Siewert J. Marrink, Matthew M. Heberling, Gjalt G. Wybenga, Biotechnology, X-ray Crystallography, and Molecular Dynamics
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Models, Molecular ,Ammonia-Lyases ,ORGANIC-SOLVENTS ,Stereochemistry ,Protein Conformation ,COSOLVENT MIXTURES ,Phenylalanine ,Phenylalanine ammonia-lyase ,Molecular Dynamics Simulation ,Crystallography, X-Ray ,Biochemistry ,Residue (chemistry) ,LACCASE ,stomatognathic system ,Catalytic Domain ,parasitic diseases ,MUTATIONAL ANALYSIS ,CATALYTIC-ACTIVITY ,BETA-AMINO ACIDS ,Intramolecular Transferases ,Inner loop ,Phenylalanine Ammonia-Lyase ,chemistry.chemical_classification ,Chemistry ,Temperature ,General Medicine ,Lyase ,FAMILY ,Amino acid ,Enzyme ,Molecular Medicine ,ENZYMES - Abstract
Deciphering the structural features that functionally separate ammonia lyases from aminomutases is of interest because it may allow for the engineering of more efficient aminomutases for the synthesis of unnatural amino acids (e.g., beta-amino acids). However, this has proved to be a major challenge that involves understanding the factors that influence their activity and regioselectivity differences. Herein, we report evidence of a structural determinant that dictates the activity differences between a phenylalanine ammonia lyase (PAL) and aminomutase (PAM). An inner loop region that closes the active sites of both PAM and PAL was mutated within PAM (PAM residues 77-97) in a stepwise approach to study the effects when the equivalent residue(s) found in the PAL loop were introduced into the PAM loop. Almost all of the single loop mutations triggered a lyase phenotype in PAM. Experimental and computational evidence suggest that the induced lyase features result from inner loop mobility enhancements, which are possibly caused by a 3(10)-helix cluster, flanking a-helices, and hydrophobic interactions. These findings pinpoint the inner loop as a structural determinant of the lyase and mutase activities of PAM.
- Published
- 2014
229. Global structural changes of an ion channel during its gating are followed by ion mobility mass spectrometry
- Author
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Frank Sobott, Armagan Kocer, Duygu Yilmaz, Zhuolun Li, Anna Dimitrova, Siewert J. Marrink, Helgi I. Ingólfsson, Albert Konijnenberg, Catherine Vénien-Bryan, Department of Chemistry, University Medical Center [Utrecht]-Biomolecular & Analytical Mass Spectrometry group, Department of Neuroscience, University of Groningen [Groningen], Institut de minéralogie, de physique des matériaux et de cosmochimie (IMPMC), Muséum national d'Histoire naturelle (MNHN)-Institut de recherche pour le développement [IRD] : UR206-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Molecular Dynamics, and Molecular Neuroscience and Ageing Research (MOLAR)
- Subjects
CONFORMATIONAL-CHANGES ,Ion-mobility spectrometry ,Octoxynol ,Protein Conformation ,[SDV]Life Sciences [q-bio] ,Detergents ,membrane proteins ,Gating ,Molecular Dynamics Simulation ,010402 general chemistry ,Mass spectrometry ,01 natural sciences ,Mechanotransduction, Cellular ,Ion Channels ,Mass Spectrometry ,PROTEIN COMPLEXES ,03 medical and health sciences ,Protein structure ,COARSE-GRAINED MODEL ,structure function ,Escherichia coli ,Lipid bilayer ,Ion channel ,030304 developmental biology ,0303 health sciences ,Multidisciplinary ,Chemistry ,MEMBRANE-PROTEINS ,Escherichia coli Proteins ,fungi ,MACROMOLECULAR ASSEMBLIES ,Biological Sciences ,ion channel gating ,MSCL ,0104 chemical sciences ,Crystallography ,Microscopy, Electron ,ion mobility mass spectrometry ,Membrane protein ,MOLECULAR-DYNAMICS ,ESCHERICHIA-COLI ,Biophysics ,FORCE-FIELD ,Mechanosensitive channels ,MECHANOSENSITIVE CHANNEL ,Engineering sciences. Technology - Abstract
International audience; Mechanosensitive ion channels are sensors probing membrane tension in all species; despite their importance and vital role in many cell functions, their gating mechanism remains to be elucidated. Here, we determined the conditions for releasing intact mechanosensitive channel of large conductance (MscL) proteins from their detergents in the gas phase using native ion mobility-mass spectrometry (IM-MS). By using IM-MS, we could detect the native mass of MscL from Escherichia coli, determine various global structural changes during its gating by measuring the rotationally averaged collision cross-sections, and show that it can function in the absence of a lipid bilayer. We could detect global conforma-tional changes during MscL gating as small as 3%. Our findings will allow studying native structure of many other membrane proteins.
- Published
- 2014
230. Simulation of gel phase formation and melting in lipid bilayers using a coarse grained model
- Author
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Alan E. Mark, Siewert J. Marrink, Jelger Risselada, Groningen Biomolecular Sciences and Biotechnology, Molecular Dynamics, and Faculty of Science and Engineering
- Subjects
Models, Molecular ,LATERAL DIFFUSION ,1,2-Dipalmitoylphosphatidylcholine ,Lipid Bilayers ,Analytical chemistry ,Nucleation ,order-disorder ,PRESSURE ,MEMBRANES ,Biochemistry ,Phase Transition ,PHOSPHATIDYLCHOLINES ,Phase (matter) ,DIPALMITOYLPHOSPHATIDYLCHOLINE ,Monolayer ,WATER ,Lipid bilayer ,Molecular Biology ,membrane ,main phase transition ,heterophase fluctuations ,nucleation and growth ,Chemistry ,Transition temperature ,Bilayer ,Organic Chemistry ,Temperature ,hexatic phase ,Cell Biology ,molecular dynamics ,PHOSPHOLIPIDS ,Chemical physics ,MOLECULAR-DYNAMICS ,NMR-SPECTROSCOPY ,DPPC ,Crystallization ,Hexatic phase ,Gels ,Order of magnitude ,NUCLEATION - Abstract
The transformation between a gel and a fluid phase in dipalmitoyl-phosphatidylcholine (DPPC) bilayers has been simulated using a coarse grained (CG) model by cooling bilayer patches composed of up to 8000 lipids. The critical step in the transformation process is the nucleation of a gel cluster consisting of 20-80 lipids, spanning both monolayers. After the formation of the critical cluster, a fast growth regime is entered. Growth slows when multiple gel domains start interacting, forming a percolating network. Long-lived fluid domains remain trapped and can be metastable on a microsecond time scale. From the temperature dependence of the rate of cluster growth, the line tension of the fluid-gel interface was estimated to be 3 +/- 2 pN. The reverse process is observed when heating the gel phase. No evidence is found for a hexatic phase as an intermediate stage of melting. The hysteresis observed in the freezing and melting transformation is found to depend both on the system size and on the time scale of the simulation. Extrapolating to macroscopic length and time scales, the transition temperature for heating and cooling converges to 295 +/- 5 K, in semi-quantitative agreement with the experimental value for DPPC (315 K). The phase transformation is associated with a drop in lateral mobility of the lipids by two orders of magnitude, and an increase in the rotational correlation time of the same order of magnitude. The lipid headgroups, however, remain fluid. These observations are in agreement with experimental findings, and show that the nature of the ordered phase obtained with the CG model is indeed a gel rather than a crystalline phase. Simulations performed at different levels of hydration furthermore show that the gel phase is stabilized at low hydration. A simulation of a small DPPC vesicle reveals that curvature has the opposite effect. (c) 2005 Elsevier Ireland Ltd. All rights reserved.
- Published
- 2005
231. Molecular structure of the lecithin ripple phase
- Author
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S. Yefimov, Alex H. de Vries, Alan E. Mark, Siewert J. Marrink, Groningen Biomolecular Sciences and Biotechnology, Molecular Dynamics, and Theoretical Chemistry
- Subjects
P-BETA' ,food.ingredient ,1,2-Dipalmitoylphosphatidylcholine ,Ripple ,Lipid Bilayers ,Static Electricity ,TRANSITIONS ,MEMBRANES ,Lecithin ,Quantitative Biology::Cell Behavior ,Quantitative Biology::Subcellular Processes ,Molecular dynamics ,food ,Phase (matter) ,Static electricity ,THERMODYNAMICS ,Molecule ,WATER-SYSTEM ,Computer Simulation ,Lipid bilayer ,LIPID-BILAYERS ,Physics::Biological Physics ,structural model ,GEL ,Multidisciplinary ,Chemistry ,DYNAMICS SIMULATIONS ,Water ,Biological Sciences ,Condensed Matter::Soft Condensed Matter ,PHOSPHOLIPIDS ,CRYSTALS ,Crystallography ,Membrane ,molecular dynamics simulation ,Models, Chemical ,Chemical physics ,Phosphatidylcholines ,lipids (amino acids, peptides, and proteins) ,Gels - Abstract
Molecular dynamics simulations of lecithin lipid bilayers in water as they are cooled from the liquid crystalline phase show the spontaneous formation of rippled bilayers. The ripple consists of two domains of different length and orientation, connected by a kink. The organization of the lipids in one domain of the ripple is found to be that of a splayed gel; in the other domain the lipids are gel-like and fully interdigitated. In the concave part of the kink region between the domains the lipids are disordered. The results are consistent with the experimental information available and provide an atomic-level model that may be tested by further experiments.
- Published
- 2005
232. Coarse grained model for semiquantitative lipid simulations
- Author
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Alan E. Mark, Siewert J. Marrink, de Alex Vries, Groningen Biomolecular Sciences and Biotechnology, Molecular Dynamics, and Theoretical Chemistry
- Subjects
LATERAL DIFFUSION ,BILAYERS ,MOLECULAR-DYNAMICS SIMULATIONS ,Bilayer ,Dissipative particle dynamics ,Hexagonal phase ,Thermodynamics ,Decane ,Permeation ,MEMBRANE-FUSION ,SURFACTANT SOLUTIONS ,Micelle ,Surfaces, Coatings and Films ,PHOSPHOLIPIDS ,chemistry.chemical_compound ,Crystallography ,AMPHIPHILIC MESOPHASES ,chemistry ,Dipalmitoylphosphatidylcholine ,Materials Chemistry ,Compressibility ,DISSIPATIVE PARTICLE DYNAMICS ,WATER ,Physical and Theoretical Chemistry ,COMPUTER-SIMULATIONS - Abstract
This paper describes the parametrization of a new coarse grained (CG) model for lipid and surfactant systems. Reduction of the number of degrees of freedom together with the use of short range potentials makes it computationally very efficient. Compared to atomistic models a gain of 3-4 orders of magnitude can be achieved. Micrometer length scales or millisecond time scales are therefore within reach. To encourage applications, the model is kept very simple. Only a small number of coarse grained atom types are defined, which interact using a few discrete levels of interaction. Despite the computational speed and the simplistic nature of the model, it proves to be both versatile in its applications and accurate in its predictions. We show that densities of liquid alkanes from decane up to eicosane can be reproduced to within 5%, and the mutual solubilities of alkanes in water and water in alkanes can be reproduced within 0.5 kT of the experimental values. The CG model for dipalmitoylphosphatidylcholine (DPPC) is shown to aggregate spontaneously into a bilayer. Structural properties such as the area per headgroup and the phosphate-phosphate distance match the experimentally measured quantities closely. The same is true for elastic properties such as the bending modulus and the area compressibility, and dynamic properties such as the lipid lateral diffusion coefficient and the water permeation rate. The distribution of the individual lipid components along the bilayer normal is very similar to distributions obtained from atomistic simulations. Phospholipids with different headgroup (ethanolamine) or different tail lengths (lauroyl, stearoyl) or unsaturated tails (oleoyl) can also be modeled with the CG force field. The experimental area per headgroup can be reproduced for most lipids within 0.02 nm(2). Finally, the CG model is applied to nonbilayer phases. Dodecylphosphocholine (DPC) aggregates into small micelles that are structurally very similar to ones modeled atomistically, and DOPE forms an inverted hexagonal phase with structural parameters in agreement with experimental data.
- Published
- 2004
233. Extending the Adress Multiscale Scheme for Protein and Bilayer Applications
- Author
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Siewert J. Marrink, Matej Praprotnik, Manuel N. Melo, and Julija Zavadlav
- Subjects
Scheme (programming language) ,Single site ,Computer science ,Adaptive resolution ,Bilayer ,Resolution (electron density) ,Biophysics ,Focus (optics) ,Biological system ,computer ,computer.programming_language - Abstract
The Adaptive Resolution Scheme (AdResS) for multiscale simulations has been successfully used in simulations of solutes in isotropic solvents. In this scheme the system is described by regions of coarse- and fine-grain (CG and FG) resolution, connected by a hybrid resolution region.In spite of the successful applications, systems where a lipid bilayer extends across resolution regions remain, however, outside the scope of AdResS. The scheme cannot currently cope with molecules that span resolution boundaries at the coarser level. Up until now most AdResS applications used solvents that can be represented at the coarser resolution using a single site, thus obviating the limitation of the scheme.In this work we describe the extension of AdResS to allow the simulation of solvents with multiple CG sites, with focus on the case of a lipid bilayer. To this end, lipid bonded interactions were included in the AdResS FC-CG interaction transformation.The successful extension of AdResS to lipids further prompted the study of systems where proteins too can cross resolution barriers.
- Published
- 2016
234. Molecular dynamics simulation of the formation, structure, and dynamics of small phospholipid vesicles
- Author
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Alan E. Mark, Siewert J. Marrink, Groningen Biomolecular Sciences and Biotechnology, and Molecular Dynamics
- Subjects
SELF-ASSEMBLED MEMBRANES ,LATERAL DIFFUSION ,1,2-Dipalmitoylphosphatidylcholine ,Stereochemistry ,TENSION ,Phospholipid ,Model lipid bilayer ,Biochemistry ,Catalysis ,ENERGY ,Molecular dynamics ,chemistry.chemical_compound ,Colloid and Surface Chemistry ,FUSION ,Monolayer ,LENGTH ,Computer Simulation ,Lipid bilayer ,LIPID-BILAYERS ,Phospholipids ,Chemistry ,Bilayer ,Vesicle ,ELASTICITY ,UNDULATIONS ,General Chemistry ,MODEL ,Models, Chemical ,Dipalmitoylphosphatidylcholine ,Liposomes ,Biophysics ,lipids (amino acids, peptides, and proteins) - Abstract
Here, we use coarse grained molecular dynamics (MD) simulations to study the spontaneous aggregation of dipalmitoylphosphatidylcholine (DPPC) lipids into small unilamellar vesicles. We show that the aggregation process occurs on a nanosecond time scale, with bicelles and cuplike vesicles formed at intermediate stages. Formation of hemifused vesicles is also observed at higher lipid concentration. With either 25% dipalmitoylphosphatidylethanolamine (DPPE) or lysoPC mixed into the system, the final stages of the aggregation process occur significantly faster. The structure of the spontaneously formed vesicles is analyzed in detail. Microsecond simulations of isolated vesicles reveal significant differences in the packing of the lipids between the inner and outer monolayers, and between PC, PE, and lysoPC. Due to the small size of the vesicles they remain almost perfectly spherical, undergoing very limited shape fluctuations or bilayer undulations. The lipid lateral diffusion rate is found to be faster in the outer than in the inner monolayer. The water permeability coefficient of the pure DPPC vesicles is of the order of 10(-3) cm s(-1), in agreement with experimental measurements.
- Published
- 2003
235. Simulation of MscL Gating in a bilayer under stress
- Author
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Alan E. Mark, Giorgio Colombo, Siewert J. Marrink, Groningen Biomolecular Sciences and Biotechnology, and Molecular Dynamics
- Subjects
Models, Molecular ,ESCHERICHIA-COLI-CELLS ,MECHANISM ,Cell Membrane Permeability ,MOLECULAR-DYNAMICS SIMULATIONS ,Compressive Strength ,Membrane Fluidity ,Protein Conformation ,Lipid Bilayers ,Biophysics ,Large-conductance mechanosensitive channel ,PROTEIN ,ION-CHANNEL ,Gating ,PRESSURE ,Mechanotransduction, Cellular ,TRANSDUCTION ,Protein Structure, Secondary ,Motion ,Molecular dynamics ,Channels, Receptors, and Transporters ,Biomimetics ,Tensile Strength ,CONDUCTANCE MECHANOSENSITIVE CHANNEL ,Membrane fluidity ,Computer Simulation ,Lipid bilayer ,Ion channel ,Chemistry ,Bilayer ,Water ,Conductance ,MEMBRANE TENSION ,Protein Subunits ,Crystallography ,Phosphatidylcholines ,Stress, Mechanical ,MYCOBACTERIUM-TUBERCULOSIS ,Hydrophobic and Hydrophilic Interactions ,Ion Channel Gating ,Porosity - Abstract
The initial stages of the gating of the mechanoselective channel of large conductance from Mycobacterium tuberculosis have been studied in atomic detail using molecular dynamics simulation techniques. A truncated form of the protein complex embedded in a palmitoyloleoylphosphatidylcholine lipid bilayer and surrounded by explicit water was simulated under different pressure conditions to mimic the effects of tension and compression within the membrane on the protein. As a direct result of lateral tension being applied to the membrane, an increase in the tilt of a subset of the transmembrane helices was observed. This in turn led to the enlargement of the pore and the disruption of the hydrophobic gate consisting of residues Ile-14 and Val-21. The simulations suggest that opening occurs in a sequential staged process. Such a mechanism could explain the partial opening or staged conductance observed in patch-clamp experiments using related large conductance mechanosensitive channel complexes.
- Published
- 2003
236. Molecular dynamics simulations of mixed micelles modeling human bile
- Author
-
Siewert J. Marrink, Alan E. Mark, Groningen Biomolecular Sciences and Biotechnology, and Moleculaire Dynamica
- Subjects
Models, Molecular ,Phospholipid ,Salt (chemistry) ,ORGANIZATION ,Biochemistry ,Micelle ,Bile Acids and Salts ,chemistry.chemical_compound ,Molecular dynamics ,Phosphatidylcholine ,PHOSPHATIDYLCHOLINE ,Bile ,Humans ,Organic chemistry ,SCATTERING ,Computer Simulation ,GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries) ,Micelles ,Phospholipids ,chemistry.chemical_classification ,BILIARY LIPID SYSTEMS ,Aqueous solution ,Chemistry ,Bilayer ,CHOLESTEROL ,SALT ,Water ,BILAYER ,Membrane ,Chemical physics ,PRECIPITATION ,ComputingMethodologies_DOCUMENTANDTEXTPROCESSING ,Thermodynamics ,lipids (amino acids, peptides, and proteins) ,MEMBRANE - Abstract
Extensive molecular dynamics (MD) simulations of binary systems of phospholipids and bile salts, a model for human bile, have been performed. Recent progress in hardware and software development allows simulation of the spontaneous aggregation of the constituents into small mixed micelles, in agreement with experimental observations. The MD simulations reveal the structure of these micelles at atomic detail. The phospholipids are packed radially with their headgroups at the surface and the hydrophobic tails pointing toward the micellar center. The bile salts act as wedges between the phospholipid headgroups, with their hydrophilic sides exposed to the aqueous environment. The structure of the micelles strongly resembles the previously proposed radial shell model. Simulations including small fractions of cholesterol reveal how cholesterol is solubilized inside these mixed micelles without changing their overall structure.
- Published
- 2002
237. Lipid and Peptide Diffusion in Bilayers
- Author
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Brian A. Camley, Frank L. H. Brown, Michael G. Lerner, Bradley S. Perrin, Richard W. Pastor, Siewert J. Marrink, Richard M. Venable, Helgi I. Ingólfsson, Enzymology, and Molecular Dynamics
- Subjects
0301 basic medicine ,1,2-Dipalmitoylphosphatidylcholine ,Surface Properties ,Dimer ,Lipid Bilayers ,Analytical chemistry ,Thermodynamics ,Molecular Dynamics Simulation ,01 natural sciences ,Article ,Diffusion ,03 medical and health sciences ,chemistry.chemical_compound ,0103 physical sciences ,Materials Chemistry ,Periodic boundary conditions ,Physical and Theoretical Chemistry ,Diffusion (business) ,Particle Size ,010304 chemical physics ,Gramicidin ,Fick's laws of diffusion ,Surfaces, Coatings and Films ,030104 developmental biology ,Monomer ,Saffman–Delbrück model ,chemistry ,Dipalmitoylphosphatidylcholine ,Yield (chemistry) - Abstract
The Periodic Safmann-Delbrück (PSD) model, an extension of the Safmann-Delbrück model developed to describe the effects of periodic boundary conditions on the diffusion constants of lipids and proteins obtained from simulation, is tested using the coarse-grained Martini and all-atom CHARMM36 (C36) force fields. Simulations of pure Martini dipalmitoylphosphatidylcholine (DPPC) bilayers and those with one embedded gramicidin A (gA) dimer or one gA monomer with sizes ranging from 512 to 2048 lipids support the PSD model. Underestimates of D^∞ (the value of the diffusion constant for an infinite system) from the 512 lipid system are 35% for DPPC, 45% for the gA monomer, and 70% for the gA dimer. Simulations of all-atom DPPC and dioleoylphosphatidylcholine (DOPC) bilayers yield diffusion constants not far from experiment. However, the PSD model predicts that diffusion constants at the sizes of the simulation should underestimate experiment by approximately a factor of 3 for DPPC and 2 for DOPC. This likely implies a deficiency in the C36 force field. A Bayesian-based method for extrapolating diffusion constants of lipids and proteins in membranes obtained from simulation to infinite system size is provided.
- Published
- 2017
238. Curvature-Induced Lipid Sorting in Plasma Membrane Tethers
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Helgi I. Ingólfsson, D. Peter Tieleman, Svetlana Baoukina, Siewert J. Marrink, and Molecular Dynamics
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Chemistry ,Bilayer ,Biophysics ,Plasma ,Curvature ,Molecular dynamics ,Crystallography ,Membrane ,Phase (matter) ,ComputingMethodologies_DOCUMENTANDTEXTPROCESSING ,Lipid bilayer phase behavior ,Lipid bilayer ,GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries) - Abstract
Membrane tethers are nanotubes formed by lipid bilayers. They are efficient structures for cellular transport and communication, and for storage of excess membrane area. Previous tether pulling experiments provided insights on membrane mechanical properties, and the curvature effects on phase behaviour and distribution of coexisting phases. However, detailed information on tether properties and variations in composition is challenging to obtain experimentally due to the small diameters and dynamic nature of tethers.Here we provide a molecular view on curvature-induced lipid sorting in plasma membrane tethers. We pulled tethers from an idealized plasma membrane model using molecular dynamics simulations with the coarse-grained Martini model. The membrane consists of 63 lipid types with an asymmetric distribution of components between the leaflets [JACS, 2014, 136, 14554]. The tethers are formed by applying an external constant force to a lipid patch in the direction normal to the bilayer plane [Biophys J, 1012, 102, 1866]. Pulling is performed both from the inner and outer leaflets, corresponding to the direction in and out of the cell, respectively. As a result of pulling, we observe re-distribution of different lipid types along the regions of different curvature without macroscopic phase separation. Depending on the direction of pulling, the distribution of lipids and the tether properties differ.
- Published
- 2017
239. Curvature-Dependent Elastic Properties of Liquid-Ordered Domains Result in Inverted Domain Sorting on Uniaxially Compressed Vesicles
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Siewert J. Marrink, H. Jelger Risselada, Marcus Mueller, Groningen Biomolecular Sciences and Biotechnology, and Molecular Dynamics
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Models, Molecular ,Materials science ,PROTEINS ,General Physics and Astronomy ,Bending ,010402 general chemistry ,Curvature ,01 natural sciences ,Phase Transition ,Quantitative Biology::Subcellular Processes ,ENERGY ,03 medical and health sciences ,Phase (matter) ,FIELD ,Unilamellar Liposomes ,030304 developmental biology ,0303 health sciences ,Vesicle ,CHOLESTEROL ,Sorting ,Flexural rigidity ,Elasticity ,SIMULATIONS ,0104 chemical sciences ,Condensed Matter::Soft Condensed Matter ,MODEL ,BOUNDARY ,Chemical physics ,Domain (ring theory) ,Compressibility ,Thermodynamics ,SHAPE ,MEMBRANE ,LIPIDS - Abstract
Using a coarse-grained molecular model we study the spatial distribution of lipid domains on a 20-nm-sized vesicle. The lipid mixture laterally phase separates into a raftlike, liquid-ordered (l(o)) phase and a liquid-disordered phase. As we uniaxially compress the mixed vesicle keeping the enclosed volume constant, we impart tension onto the membrane. The vesicle adopts a barrel shape, which is composed of two flat contact zones and a curved edge. The l(o) domain, which exhibits a higher bending rigidity, segregates to the highly curved edge. This inverted domain sorting switches to normal domain sorting, where the l(o) domain prefers the flat contact zone, when we release the contents of the vesicle. We rationalize this domain sorting by a pronounced reduction of the bending rigidity and area compressibility of the l(o) phase upon bending.
- Published
- 2011
240. The activation mode of the mechanosensitive ion channel, MscL, by lysophosphatidylcholine differs from tension-induced gating
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Siewert J. Marrink, Jan Peter Birkner, Anna Dimitrova, Clement Arnarez, Martin Walko, Armagan Kocer, Helgi I. Ingólfsson, Mac Donald F. Jose, Nobina Mukherjee, Zernike Institute for Advanced Materials, Molecular Dynamics, and Molecular Neuroscience and Ageing Research (MOLAR)
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spectroscopy ,Lipid Bilayers ,Molecular Sequence Data ,FUNCTIONAL RECONSTITUTION ,Gating ,Biochemistry ,Mechanotransduction, Cellular ,Ion Channels ,Research Communications ,Mechanosensitive ion channel ,COARSE-GRAINED MODEL ,Genetics ,mechanosensation ,Protein–lipid interaction ,Amino Acid Sequence ,Lipid bilayer ,LIPID-BILAYERS ,Molecular Biology ,Ion channel ,Mechanosensation ,Chemistry ,MEMBRANE-PROTEINS ,Escherichia coli Proteins ,fungi ,SINGLE RESIDUE ,Conductance ,Lysophosphatidylcholines ,protein-lipid interaction ,SIMULATIONS ,Crystallography ,13. Climate action ,ESCHERICHIA-COLI ,MOLECULAR-DYNAMICS ,critical micelle concentration of LPC ,Biophysics ,FORCE-FIELD ,Mechanosensitive channels ,lipids (amino acids, peptides, and proteins) ,MYCOBACTERIUM-TUBERCULOSIS ,Ion Channel Gating ,Biotechnology - Abstract
One of the best-studied mechanosensitive channels is the mechanosensitive channel of large conductance (MscL). MscL senses tension in the membrane evoked by an osmotic down shock and directly couples it to large conformational changes leading to the opening of the channel. Spectroscopic techniques offer unique possibilities to monitor these conformational changes if it were possible to generate tension in the lipid bilayer, the native environment of MscL, during the measurements. To this end, asymmetric insertion of l-α-lysophosphatidylcholine (LPC) into the lipid bilayer has been effective; however, how LPC activates MscL is not fully understood. Here, the effects of LPC on tension-sensitive mutants of a bacterial MscL and on MscL homologs with different tension sensitivities are reported, leading to the conclusion that the mode of action of LPC is different from that of applied tension. Our results imply that LPC shifts the free energy of gating by interfering with MscL-membrane coupling. Furthermore, we demonstrate that the fine-tuned addition of LPC can be used for controlled activation of MscL in spectroscopic studies.—Mukherjee, N., Jose, M. D., Birkner, J. P., Walko, M., Ingolfsson, H. I., Dimitrova, A., Arnarez, C., Marrink, S. J., Kocer, A. The activation mode of the mechanosensitive ion channel, MscL, by lysophosphatidylcholine differs from tension-induced gating.
- Published
- 2014
241. Establishing conditions for simulating hydrophobic solutes in electric fields by molecular dynamics
- Author
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Zoran Miličević, Siewert J. Marrink, David M. Smith, Ana-Sunčana Smith, and Molecular Dynamics
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GROMACS ,Molecular dynamics ,BATH ,Catalysis ,Inorganic Chemistry ,symbols.namesake ,ARTIFACTS ,SYSTEMS ,Electrophoretic mobility ,Stokes' law ,Quantum mechanics ,Electric field ,WATER ,Physical and Theoretical Chemistry ,Range (particle radiation) ,Van der Waals interactions ,Chemistry ,Organic Chemistry ,Computer Science Applications ,Electrophoresis ,SIZE ,Computational Theory and Mathematics ,Chemical physics ,symbols ,Particle ,Net force ,van der Waals force ,CHARGE - Abstract
Despite considerable effort over the last decade, the interactions between solutes and solvents in the presence of electric fields have not yet been fully understood. A very useful manner in which to study these systems is through the application of molecular dynamics (MD) simulations. However, a number of MD studies have shown a tremendous sensitivity of the migration rate of a hydrophobic solute to the treatment of the long range part of the van der Waals interactions. While the origin of this sensitivity was never explained, the mobility is currently regarded as an artifact of an improper simulation setup. We explain the spread in observed mobilites by performing extensive molecular dynamics simulations using the GROMACS software package on a system consisting of a model hydrophobic object (Lennard-Jones particle) immersed in water both in the presence and absence of a static electric field. We retrieve a unidirectional field-induced mobility of the hydrophobic object when the forces are simply truncated. Careful analysis of the data shows that, only in the specific case of truncated forces, a non-zero van der Waals force acts, on average, on the Lennard-Jones particle. Using the Stokes law we demonstrate that this force yields quantitative agreement with the field-induced mobility found within this setup. In contrast, when the treatment of forces is continuous, no net force is observed. In this manner, we provide a simple explanation for the previously controversial reports.
- Published
- 2014
242. Hydrophobic compounds reshape membrane domains
- Author
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Luca Monticelli, Jonathan Barnoud, Siewert J. Marrink, Giulia Rossi, and Molecular Dynamics
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Biophysical Simulations ,Cell Membranes ,Biophysics ,Biology ,Molecular Dynamics Simulation ,010402 general chemistry ,Molecular Dynamics ,01 natural sciences ,Biochemistry ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Molecular dynamics ,Membrane Microdomains ,Computational Chemistry ,Genetics ,Molecule ,Computer Simulation ,Organic Chemicals ,Molecular Biology ,lcsh:QH301-705.5 ,Ecology, Evolution, Behavior and Systematics ,030304 developmental biology ,0303 health sciences ,Ecology ,Physics ,Computational Biology ,Biology and Life Sciences ,Cell Biology ,Lipids ,0104 chemical sciences ,Chemistry ,Membrane ,Computational Theory and Mathematics ,lcsh:Biology (General) ,Modeling and Simulation ,Physical Sciences ,Lipid Bilayer ,Signal transduction ,Cellular Structures and Organelles ,Hydrophobic and Hydrophilic Interactions ,Membrane Characteristics ,Protein trafficking ,Research Article - Abstract
Cell membranes have a complex lateral organization featuring domains with distinct composition, also known as rafts, which play an essential role in cellular processes such as signal transduction and protein trafficking. In vivo, perturbations of membrane domains (e.g., by drugs or lipophilic compounds) have major effects on the activity of raft-associated proteins and on signaling pathways, but they are difficult to characterize because of the small size of the domains, typically below optical resolution. Model membranes, instead, can show macroscopic phase separation between liquid-ordered and liquid-disordered domains, and they are often used to investigate the driving forces of membrane lateral organization. Studies in model membranes have shown that some lipophilic compounds perturb membrane domains, but it is not clear which chemical and physical properties determine domain perturbation. The mechanisms of domain stabilization and destabilization are also unknown. Here we describe the effect of six simple hydrophobic compounds on the lateral organization of phase-separated model membranes consisting of saturated and unsaturated phospholipids and cholesterol. Using molecular simulations, we identify two groups of molecules with distinct behavior: aliphatic compounds promote lipid mixing by distributing at the interface between liquid-ordered and liquid-disordered domains; aromatic compounds, instead, stabilize phase separation by partitioning into liquid-disordered domains and excluding cholesterol from the disordered domains. We predict that relatively small concentrations of hydrophobic species can have a broad impact on domain stability in model systems, which suggests possible mechanisms of action for hydrophobic compounds in vivo., Author Summary Cell membranes consist of a variety of lipids and proteins with inhomogeneous lateral distribution, forming domains with distinct composition and properties. These domains play a fundamental role in a number of biological processes, and perturbing them can have important effects on cellular functions. Some chemicals with high affinity for lipid membranes perturb membrane domains, but the link between properties of the chemicals and domain perturbation is not understood. The mechanisms of domain perturbation are also not understood. In the present work we use molecular simulations of model membranes to understand the driving forces and the mechanisms of domain perturbation by different chemicals. We explore the effect of six hydrophobic compounds, all of them rather simple and common but with different size, shape, and properties. We find that all hydrophobic compounds alter the stability of domains, but not all of them in the same way. We identify two groups of compounds with opposite effects: aromatic compounds stabilize domains, while aliphatic compounds destabilize them. Simulations also allow us to visualize, for the first time, the mechanism of domain perturbation – which is very difficult to assess experimentally. Our findings on model membranes suggest possible mechanisms of action for hydrophobic chemicals in living cells.
- Published
- 2014
243. Mechanisms shaping cell membranes
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Leonid V. Chernomordik, Siewert J. Marrink, Nicole Liska, Michael M. Kozlov, Harvey T. McMahon, Felix Campelo, and Molecular Dynamics
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Organelles ,Peripheral membrane protein ,Cell Membrane ,Proteins ,Biological membrane ,Cell Biology ,Biology ,Article ,Cell biology ,Membrane bending ,Membrane ,Membrane curvature ,Biophysics ,Animals ,Integral membrane protein ,Membrane biophysics ,Hydrophobic and Hydrophilic Interactions ,Cytoskeleton ,Elasticity of cell membranes - Abstract
Membranes of intracellular organelles are characterized by large curvatures with radii of the order of 10-30nm. While, generally, membrane curvature can be a consequence of any asymmetry between the membrane monolayers, generation of large curvatures requires the action of mechanisms based on specialized proteins. Here we discuss the three most relevant classes of such mechanisms with emphasis on the physical requirements for proteins to be effective in generation of membrane curvature. We provide new quantitative estimates of membrane bending by shallow hydrophobic insertions and compare the efficiency of the insertion mechanism with those of the protein scaffolding and crowding mechanisms.
- Published
- 2014
244. A conceptual modelling for combining potentials in both coarse grain and fine grain sugar molecules
- Author
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Brighter Agyemang, Siewert J. Marrink, Dominic Damoah, Edward Danso Ansong, Nicolae Goga, and Molecular Dynamics
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Theoretical computer science ,Fine grain ,Forecfield) Coarse grain ,Computer science ,Physical phenomena ,Multiscalling ,Microscopic level ,GROMACS ,Biological system ,Force field (chemistry) ,Radial Distribution Function(RDF) - Abstract
The use of computers for experiment has offered the ability to study the behavior of substances at the microscopic level providing understanding into the physical phenomena we face. This has raised questions on resources and the mechanisms that are employed to provide effective analysis of simulation results. In view of this, various approaches in addressing these challenges have been experimented with which coarse-graining is a major factor. Coarse-grain simulations reduces the detail level of simulations but offers larger time steps and required properties, among other merits, in the modeling of complex structures like carbohydrates. This research paper provides a conceptual model whereby the potentials that result from coarse grain and fine grain simulations can be combined using the theories of multi-scaling. A demonstration of the simulation of sucrose, a carbohydrate, is provided using the martini force field for the simulation process.
- Published
- 2014
245. Adaptive resolution simulation of an atomistic protein in MARTINI water
- Author
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Julija Zavadlav, Manuel N. Melo, Siewert J. Marrink, Matej Praprotnik, and Molecular Dynamics
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General Physics and Astronomy ,SOFT MATTER ,Molecular Dynamics Simulation ,Force field (chemistry) ,Accessible surface area ,Molecular dynamics ,FLUIDS ,Computational chemistry ,BIOMOLECULAR SIMULATIONS ,SYSTEMS ,Water model ,Computer Simulation ,Soft matter ,Physical and Theoretical Chemistry ,COMPUTER-SIMULATIONS ,Quantitative Biology::Biomolecules ,Mesoscopic physics ,Chemistry ,Molecular biophysics ,HYDRATION ,Water ,Heterotrimeric GTP-Binding Proteins ,GRAINED MULTISCALE SIMULATIONS ,MOLECULAR-DYNAMICS SIMULATION ,MODEL ,Chemical physics ,Radius of gyration ,FORCE-FIELD - Abstract
We present an adaptive resolution simulation of protein G in multiscale water. We couple atomistic water around the protein with mesoscopic water, where four water molecules are represented with one coarse-grained bead, farther away. We circumvent the difficulties that arise from coupling to the coarse-grained model via a 4-to-1 molecule coarse-grain mapping by using bundled water models, i.e., we restrict the relative movement of water molecules that are mapped to the same coarse-grained bead employing harmonic springs. The water molecules change their resolution from four molecules to one coarse-grained particle and vice versa adaptively on-the-fly. Having performed 15 ns long molecular dynamics simulations, we observe within our error bars no differences between structural (e. g., root-mean-squared deviation and fluctuations of backbone atoms, radius of gyration, the stability of native contacts and secondary structure, and the solvent accessible surface area) and dynamical properties of the protein in the adaptive resolution approach compared to the fully atomistically solvated model. Our multiscale model is compatible with the widely used MARTINI force field and will therefore significantly enhance the scope of biomolecular simulations. (C) 2014 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 Unported License.
- Published
- 2014
246. Simulation of polyethylene glycol and calcium-mediated membrane fusion
- Author
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Djurre H. de Jong, Siewert J. Marrink, Martina Pannuzzo, Antonio Raudino, and Molecular Dynamics
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Models, Molecular ,MECHANISM ,POLY(ETHYLENE GLYCOL) ,Lipid Bilayers ,General Physics and Astronomy ,Polyethylene glycol ,Molecular Dynamics Simulation ,Divalent ,Polyethylene Glycols ,chemistry.chemical_compound ,CA2+ ,COARSE-GRAINED MODEL ,Polymer chemistry ,PEG ratio ,ddc:530 ,Physical and Theoretical Chemistry ,Lipid bilayer ,chemistry.chemical_classification ,Lipid bilayer fusion ,Water ,Polymer ,Adhesion ,Membrane ,chemistry ,MOLECULAR-DYNAMICS ,Biophysics ,Calcium ,Department Biologie ,PHASE-SEPARATION - Abstract
We report on the mechanism of membrane fusion mediated by polyethylene glycol (PEG) and Ca2+ by means of a coarse-grained molecular dynamics simulation approach. Our data provide a detailed view on the role of cations and polymer in modulating the interaction between negatively charged apposed membranes. The PEG chains cause a reduction of the inter-lamellar distance and cause an increase in concentration of divalent cations. When thermally driven fluctuations bring the membranes at close contact, a switch from cis to trans Ca2+-lipid complexes stabilizes a focal contact acting as a nucleation site for further expansion of the adhesion region. Flipping of lipid tails induces subsequent stalk formation. Together, our results provide a molecular explanation for the synergistic effect of Ca2+ and PEG on membrane fusion. (c) 2014 AIP Publishing LLC.
- Published
- 2014
247. Amphotericin B Versus a Reduced Toxicity Chemical Analog in Aqueous and Lipid Media: An Md Comparative Study
- Author
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Iván Ortega-Blake, M. Cristina Vargas-González, Marcel Espinosa-Caballero, Xavier Periole, Mauricio Carrillo-Tripp, Siewert J. Marrink, and Alex H. de Vries
- Subjects
Drug ,Aqueous solution ,Chemistry ,media_common.quotation_subject ,Solvation ,Biophysics ,Sterol ,Membrane ,Computational chemistry ,Amphotericin B ,medicine ,Organic chemistry ,Potency ,lipids (amino acids, peptides, and proteins) ,Solubility ,media_common ,medicine.drug - Abstract
Amphotericin B (AmB) has been the worldwide drug of choice for the past 20 years to treat advanced systemic infections caused by a wide variety of fungi. The fact that it presents high mammal toxicity has constrained it to controlled clinical use only. The search for an alternative safer drug has recently produced a chemical analog, A21, which maintains potency against fungi but presents reduced side effects on mammals compared to AmB. We believe that the increase in selectivity of the new drug is due to changes in its solubility and how it interacts with sterol molecules in the biomembranes. In this study, a set of molecular dynamics simulations were performed in order to understand the different behavior seen between AmB and A21 on a cell membrane at atomic resolution. First, we report the results of solvation free energy calculations, which allow us to estimate the partition coefficient between two media for both antibiotics. Also, the aggregation state is believed to be important for the introduction of the drug to the membrane, thus its fungicide efficacy. For this reason, a series of calculations on the free energy of transfer from aqueous to lipid media has been done for these molecules, taking into account different drug configurations and aggregation states.
- Published
- 2014
- Full Text
- View/download PDF
248. Molecular dynamics simulation of a lipid diamond cubic phase
- Author
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Siewert J. Marrink, D.P Tieleman, Groningen Biomolecular Sciences and Biotechnology, and Moleculaire Dynamica
- Subjects
Models, Molecular ,Lipid Bilayers ,Molecular Conformation ,MESOPHASE ,engineering.material ,DIAGRAM ,Biochemistry ,Catalysis ,Glycerides ,Surface-Active Agents ,Molecular dynamics ,Colloid and Surface Chemistry ,Phase (matter) ,Molecule ,Computer Simulation ,Lamellar structure ,Diamond cubic ,GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries) ,RELEASE ,Minimal surface ,Chemistry ,Bilayer ,Diamond ,MONOOLEIN/WATER SYSTEM ,General Chemistry ,Condensed Matter::Soft Condensed Matter ,Crystallography ,Models, Chemical ,Chemical physics ,ComputingMethodologies_DOCUMENTANDTEXTPROCESSING ,engineering - Abstract
This paper presents the first atomistic simulation of a cubic membrane phase. Using the molecular dynamics simulation technique both the global and the local organization of glycerolmonoolein molecules inside the diamond cubic phase are studied. Multinanosecond simulations reveal that the center of the cubic bilayer remains close to the infinite periodic minimal surface that describes the diamond geometry. We further show that the equilibrium structure of the surfactant molecules inside the cubic phase is very similar to their structure inside a simulated lamellar bilayer. The small differences arise from the packing constraints of the surfactants within the cubic phase which has an area per surfactant that increases toward the bilayer center.
- Published
- 2001
249. [Untitled]
- Author
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Wolf Val Pinczewski, Adrian Sheppard, Siewert J. Marrink, Muhammad Sahimi, and Mark Knackstedt
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Materials science ,Hydrogeology ,Capillary action ,General Chemical Engineering ,Percolation ,Mineralogy ,Mechanics ,Two-phase flow ,Saturation (chemistry) ,Residual ,Porous medium ,Fractal dimension ,Catalysis - Abstract
The invasion percolation model is used to investigate the effect of correlated heterogeneity on capillary dominated displacements in porous media. The breakthrough and residual saturations are shown to be strongly influenced by the correlations. Correlated heterogeneity leads to lower residual saturations than those observed in random systems and the scatter commonly observed in laboratory core measurements of the residual saturations can be attributed to the presence of such heterogeneity at the pore scale. Invasion percolation computations on elongated lattices, those with a geometry of Ld−1 × nL where n denotes the aspect ratio, show that residual saturations for systems with correlated heterogeneity exhibit a strong dependence on aspect ratio. This effect is not considered by experimentalists who advocate the use of long (high aspect ratio) cores in order to overcome “end-effects” in experiments on shorter cores. A new scaling law is proposed for the residual saturations in elongated systems with correlated heterogeneity, and is confirmed by numerical simulations.
- Published
- 2001
250. Partitioning of Lipids at Domain Boundaries in Model Membranes
- Author
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Siewert J. Marrink, Lars V. Schäfer, Groningen Biomolecular Sciences and Biotechnology, Zernike Institute for Advanced Materials, and Molecular Dynamics
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Biophysical Letter ,Chemistry ,Vesicle ,Lipid Bilayers ,Biophysics ,Membranes, Artificial ,Biological membrane ,HYBRID LIPIDS ,Lipids ,Domain (mathematical analysis) ,VESICLES ,Molecular dynamics ,Membrane Microdomains ,Membrane ,Biochemistry ,PLASMA-MEMBRANES ,Thermodynamics ,Molecule ,Computer Simulation ,Lipid bilayer ,RAFTS ,PHASE-SEPARATION - Abstract
Line-active molecules (“linactants”) that bind to the boundary interface between different fluid lipid domains in membranes have a strong potential as regulators of the lateral heterogeneity that is important for many biological processes. Here, we use molecular dynamics simulations in combination with a coarse-grain model that retains near-atomic resolution to identify lipid species that can act as linactants in a model membrane that is segregated into two lipid domains of different fluidity. Our simulations predict that certain hybrid saturated/unsaturated chain lipids can bind to the interface and lower the line tension, whereas cone-shaped lysolipids have a less pronounced effect.
- Published
- 2010
- Full Text
- View/download PDF
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