Molecular dynamics simulation of a dye molecule in the interior of a bilayer: 1,6-diphenyl-1,3,5-hexatriene in dipalmitoylphosphatidylcholine

Cascales, J.J. López; Huertas, M.L.; Torre, José Garcı́a de la

doi:10.1016/s0301-4622(96)02267-3

Cited by 26 publications

(34 citation statements)

References 22 publications

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“…14 Recent molecular dynamics studies have focused on a wide variety of molecules passively diffusing through membranes, such as water, [15][16][17] small molecules, [18][19][20][21][22][23] model drug compounds, 6,22,24,25 analgesics, [26][27][28] drug delivery systems, 29,30 dyes, 31,32 other lipids, 33,34 nanoparticles, [35][36][37] toxins, 38 small peptides, 39,40 and even transmembrane proteins. 41,42 However, only a handful of MD studies have examined amino acid-related systems and are confined to tryptophan, [43][44][45] arginine, 46,47 lysine, 47 and amino acid analogues.…”

Section: Introductionmentioning

confidence: 99%

Permeation of the three aromatic dipeptides through lipid bilayers: Experimental and computational study

Lee

Kuczera

Middaugh

et al. 2016

The Journal of Chemical Physics

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The time-resolved parallel artificial membrane permeability assay with fluorescence detection and comprehensive computer simulations are used to study the passive permeation of three aromatic dipeptides—N-acetyl-phenylalanineamide (NAFA), N-acetyltyrosineamide (NAYA), and N-acetyl-tryptophanamide (NATA) through a 1,2-dioleoyl-sn-glycero-3-phospocholine (DOPC) lipid bilayer. Measured permeation times and permeability coefficients show fastest translocation for NAFA, slowest for NAYA, and intermediate for NATA under physiological temperature and pH. Computationally, we perform umbrella sampling simulations to model the structure, dynamics, and interactions of the peptides as a function of z, the distance from lipid bilayer. The calculated profiles of the potential of mean force show two strong effects—preferential binding of each of the three peptides to the lipid interface and large free energy barriers in the membrane center. We use several approaches to calculate the position-dependent translational diffusion coefficients D(z), including one based on numerical solution the Smoluchowski equation. Surprisingly, computed D(z) values change very little with reaction coordinate and are also quite similar for the three peptides studied. In contrast, calculated values of sidechain rotational correlation times τrot(z) show extremely large changes with peptide membrane insertion—values become 100 times larger in the headgroup region and 10 times larger at interface and in membrane center, relative to solution. The peptides’ conformational freedom becomes systematically more restricted as they enter the membrane, sampling α and β and C7eq basins in solution, α and C7eq at the interface, and C7eq only in the center. Residual waters of solvation remain around the peptides even in the membrane center. Overall, our study provides an improved microscopic understanding of passive peptide permeation through membranes, especially on the sensitivity of rotational diffusion to position relative to the bilayer.

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Section: Introductionmentioning

confidence: 99%

Permeation of the three aromatic dipeptides through lipid bilayers: Experimental and computational study

Lee

Kuczera

Middaugh

et al. 2016

The Journal of Chemical Physics

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“…Probably due to its importance, DPH was the first probe to be studied in this way. In a pioneering early report [21], a 72-molecule 1,2-dipalmitoyl-sn-3-glycerophosphocholine (DPPC) bilayer was simulated in the presence of either one or three DPH molecules. Its results challenged the picture of two perpendicularly oriented probe populations, as it was observed that the angle between the long molecular axis and the bilayer normal rarely was N 60°, and no in-plane perpendicular orientations were detected in a 72-molecule fluid 1,2-dipalmitoyl-sn-3-glycerophosphocholine (DPPC) bilayer.…”

Section: Introductionmentioning

confidence: 99%

Diphenylhexatriene membrane probes DPH and TMA-DPH: A comparative molecular dynamics simulation study

Canto

Robalo

Santos

et al. 2016

Biochimica et Biophysica Acta (BBA) - Biomembranes

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Fluorescence spectroscopy and microscopy have been utilized as tools in membrane biophysics for decades now. Because phospholipids are non-fluorescent, the use of extrinsic membrane probes in this context is commonplace. Among the latter, 1,6-diphenylhexatriene (DPH) and its trimethylammonium derivative (TMA-DPH) have been extensively used. It is widely believed that, owing to its additional charged group, TMA-DPH is anchored at the lipid/water interface and reports on a bilayer region that is distinct from that of the hydrophobic DPH. In this study, we employ atomistic MD simulations to characterize the behavior of DPH and TMA-DPH in 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and POPC/cholesterol (4:1) bilayers. We show that although the dynamics of TMA-DPH in these membranes is noticeably more hindered than that of DPH, the location of the average fluorophore of TMA-DPH is only~3-4 Å more shallow than that of DPH. The hindrance observed in the translational and rotational motions of TMA-DPH compared to DPH is mainly not due to significant differences in depth, but to the favorable electrostatic interactions of the former with electronegative lipid atoms instead. By revealing detailed insights on the behavior of these two probes, our results are useful both in the interpretation of past work and in the planning of future experiments using them as membrane reporters.

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“…[1,2] This paper focuses on the methylene blue (MB)/dimyristoylphosphatidic acid (DMPA) Langmuir air/water monolayer system. Methylene blue is extensively used in the clinical treatment of certain tumours and non-malignant diseases by photodynamic therapy, [3] and is also relevant for technological applications, for example, as a model for adsorption of organic molecules in water depuration processes [4][5][6] and in geology for characterisation of clay mineral groups.…”

Section: Introductionmentioning

confidence: 99%

Methylene Blue Adsorption on a DMPA Lipid Langmuir Monolayer

et al. 2010

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Adsorption of methylene blue (MB) onto a dimyristoylphosphatidic acid (DMPA) Langmuir air/water monolayer is studied by molecular dynamics (MD) simulations, UV reflection spectroscopy and surface potential measurements. The free-energy profile associated with MB transfer from water to the lipid monolayer shows two minima of -66 and -60 kJ mol(-1) for its solid and gas phase, respectively, corresponding to a spontaneous thermodynamic process. From the position of the free-energy minima, it is possible to predict the precise location of MB in the interior of the DMPA monolayer. Thus, MB is accommodated in the phosphoryl or carbonyl region of the DMPA Langmuir air/water interface, depending on the isomorphic state (solid or gas phase, respectively). Reorientation of MB, measured from the bulk solution to the interior of the lipid monolayer, passes from a random orientation in bulk solution to an orientation parallel to the surface of the lipid monolayer when MB is absorbed.

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Molecular dynamics simulation of a dye molecule in the interior of a bilayer: 1,6-diphenyl-1,3,5-hexatriene in dipalmitoylphosphatidylcholine

Cited by 26 publications

References 22 publications

Permeation of the three aromatic dipeptides through lipid bilayers: Experimental and computational study

Permeation of the three aromatic dipeptides through lipid bilayers: Experimental and computational study

Diphenylhexatriene membrane probes DPH and TMA-DPH: A comparative molecular dynamics simulation study

Methylene Blue Adsorption on a DMPA Lipid Langmuir Monolayer

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