Location, Tilt, and Binding: A Molecular Dynamics Study of Voltage-Sensitive Dyes in Biomembranes

Hinner, Marlon J.; Marrink, Siewert J.; Vries, Alex H. de

doi:10.1021/jp907981y

Cited by 34 publications

(43 citation statements)

References 54 publications

(117 reference statements)

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“…The method proposed by Hinner et al 57 was used in the initial stages of parameterization. Several mapping schemes for converting atomistic representations of ceramides into CG representations were considered, differing in both the 4 assignment of atoms to beads and the number of beads used.…”

Section: Methodsmentioning

confidence: 99%

Coarse-Grain Simulations of Skin Ceramide NS with Newly Derived Parameters Clarify Structure of Melted Phase

et al. 2015

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Ceramides are lipids that are involved in numerous biologically important structures (e.g., the stratum corneum and ceramide-rich platforms) and processes (e.g., signal transduction and membrane fusion), but their behavior is not fully understood. We report coarse-grain force field parameters for N-lignocerylsphingosine (ceramide NS, also known as ceramide 2) that are consistent with the Martini force field. These parameters were optimized for simulations in the gel phase and validated against atomistic simulations. Coarse-grained simulations with our parameters provide areas per lipid, membrane thicknesses, and electron density profiles that are in good agreement with atomistic simulations. Properties of the simulated membranes are compared with available experimental data. The obtained parameters were used to model the phase behavior of ceramide NS as a function of temperature and hydration. At low water content and above the main phase transition temperature, the bilayer melts into an irregular phase, which may correspond to the unstructured melted-chain phase observed in X-ray diffraction experiments. The developed parameters also reproduce the extended conformation of ceramide, which may occur in the stratum corneum. The parameters presented herein will facilitate studies on important complex functional structures such as the uppermost layer of the skin and ceramide-rich platforms in phospholipid membranes.

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Section: Methodsmentioning

confidence: 99%

Coarse-Grain Simulations of Skin Ceramide NS with Newly Derived Parameters Clarify Structure of Melted Phase

et al. 2015

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“…It has been noted [63,61,62,23] that the solvation substitution occurring in membrane-water interfaces is often the process with the slowest relaxation to be described during the simulation of solute insertion into lipid bilayers. In accordance, we have noticed a sudden change in the hydration number of the ubiquinone tail for homologs with two or more isoprenoid units in US windows located at the membrane-water interface.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Partition, orientation and mobility of ubiquinones in a lipid bilayer

Galassi

Arantes

2015

Biochimica et Biophysica Acta (BBA) - Bioenergetics

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Ubiquinone is the universal mobile charge carrier involved in biological electron transfer processes. Its redox properties and biological function depend on the molecular partition and lateral diffusion over biological membranes. However, ubiquinone localization and dynamics within lipid bilayers are long debated and still uncertain. Here we present molecular dynamics simulations of several ubiquinone homologs with variable isoprenoid tail lengths complexed to phosphatidylcholine bilayers. Initially, a new force-field parametrization for ubiquinone is derived from and compared to high level quantum chemical data. Free energy profiles for ubiquinone insertion in the lipid bilayer are obtained with the new force-field. The profiles allow for the determination of the equilibrium location of ubiquinone in the membrane as well as for the validation of the simulation model by direct comparison with experimental partition coefficients. A detailed analysis of structural properties and interactions shows that the ubiquinone polar head group is localized at the water-bilayer interface at the same depth of the lipid glycerol groups and oriented normal to the membrane plane. Both the localization and orientation of ubiquinone head groups do not change significantly when increasing the number of isoprenoid units. The isoprenoid tail is extended and packed with the lipid acyl chains. For ubiquinones with long tails, the terminal isoprenoid units have high flexibility. Calculated ubiquinone diffusion coefficients are similar to that found for the phosphatidylcholine lipid. These results may have further implications for the mechanisms of ubiquinone transport and binding to respiratory and photosynthetic protein complexes.

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“…Depending on sampling times, a final probe distribution may converge very slowly and, therefore, it may be dependent on the choice of an initial configuration of a MD system. On the other hand, biased PMF calculations, which are rather limited in reproducing equilibrium properties, they however have an advantage of better sampling of thermodynamically unfavorable regions of the probe-bilayer system [11,25,77-79]. …”

Section: Resultsmentioning

confidence: 99%

Partitioning of 2,6-Bis(1H-Benzimidazol-2-yl)pyridine fluorophore into a phospholipid bilayer: Complementary use of fluorescence quenching studies and molecular dynamics simulations

Kyrychenko

Sevriukov

Syzova

et al. 2011

Biophysical Chemistry

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Successful use of fluorescence sensing in elucidating the biophysical properties of lipid membranes requires knowledge of the distribution and location of an emitting molecule in the bilayer. We report here that 2,6-bis(1H-benzimidazol-2-yl)pyridine (BBP), which is almost non-fluorescent in aqueous solutions, reveals a strong emission enhancement in a hydrophobic environment of a phospholipid bilayer, making it interesting for fluorescence probing of water content in a lipid membrane. Comparing the fluorescence behavior of BBP in a wide variety of solvents with those in phospholipid vesicles, we suggest that the hydrogen bonding interactions between a BBP fluorophore and water molecules play a crucial role in the observed “light switch effect”. Therefore, the loss of water-induced fluorescence quenching inside a membrane are thought to be due to deep penetration of BBP into the hydrophobic, water-free region of a bilayer. Characterized by strong quenching by transition metal ions in solution, BBP also demonstrated significant shielding from the action of the quencher in the presence of phospholipid vesicles. We used the increase in fluorescence intensity, measured upon titration of probe molecules with lipid vesicles, to estimate the partition constant and the Gibbs free energy (ΔG) of transfer of BBP from aqueous buffer into a membrane. Partitioning BBP revealed strongly favorable ΔG, which depends only slightly on the lipid composition of a bilayer, varying in a range from -6.5 to -7.0 kcal/mol. To elucidate the binding interactions of the probe with a membrane on the molecular level, a distribution and favorable location of BBP in a POPC bilayer were modeled via atomistic molecular dynamics (MD) simulations using two different approaches: (i) free, diffusion-driven partitioning of the probe molecules into a bilayer and (ii) constrained umbrella sampling of a penetration profile of the dye molecule across a bilayer. Both of these MD approaches agreed with regard to the preferred location of a BBP fluorophore within the interfacial region of a bilayer, located between the hydrocarbon acyl tails and the initial portion of the lipid headgroups. MD simulations also revealed restricted permeability of water molecules into this region of a POPC bilayer, determining the strong fluorescence enhancement observed experimentally for the membrane-partitioned form of BBP.

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Location, Tilt, and Binding: A Molecular Dynamics Study of Voltage-Sensitive Dyes in Biomembranes

Cited by 34 publications

References 54 publications

Coarse-Grain Simulations of Skin Ceramide NS with Newly Derived Parameters Clarify Structure of Melted Phase

Coarse-Grain Simulations of Skin Ceramide NS with Newly Derived Parameters Clarify Structure of Melted Phase

Partition, orientation and mobility of ubiquinones in a lipid bilayer

Partitioning of 2,6-Bis(1H-Benzimidazol-2-yl)pyridine fluorophore into a phospholipid bilayer: Complementary use of fluorescence quenching studies and molecular dynamics simulations

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