[show abstract][hide abstract] ABSTRACT: The 3alpha-hydroxyl group is a characteristic structural element of all membrane sterol molecules, while the 3-ketone group is more typically found in steroid hormones. In this work, we investigate the effect of substituting the hydroxyl group in cholesterol with the ketone group to produce ketosterone. Extensive atomistic molecular dynamics simulations of saturated lipid membranes with either cholesterol or ketosterone show that, like cholesterol, ketosterone increases membrane order and induces condensation. However, the effect of ketosterone on membrane properties is considerably weaker than that of cholesterol. This is largely due to the unstable positioning of ketosterone at the membrane-water interface, which gives rise to a small but significant number of flip-flop transitions, where ketosterone is exchanged between membrane leaflets. This is remarkable, as flip-flop motions of sterol molecules have not been previously reported in analogous lipid bilayer simulations. In the same context, ketosterone is found to be more tilted with respect to the membrane normal than cholesterol. The atomic level mechanism responsible for the increase of the steroid tilt and the promotion of flip-flops is the decrease in polar interactions at the membrane-water interface. Interactions between lipids or water and the ketone group are found to be weaker than in the case of the hydroxyl group, which allows ketosterone to penetrate through the hydrocarbon region of a membrane.
The Journal of Physical Chemistry B 03/2008; 112(7):1946-52. · 3.61 Impact Factor
[show abstract][hide abstract] ABSTRACT: Results from extensive 70 ns all-atom molecular dynamics simulations of catechol-O-methyltransferase (COMT) enzyme are reported. The simulations were performed with explicit TIP3P water and Mg2+ ions. Four different crystal structures of COMT, with and without different ligands, were used. These simulations are among the most extensive of their kind and as such served as a stability test for such simulations. On the methodological side we found that the initial energy minimization procedure may be a crucial step: particular hydrogen bonds may break, and this can initiate an irreversible loss of protein structure that becomes observable in longer time scales of the order of tens of nanoseconds. This has important implications for both molecular dynamics and quantum mechanics-molecular mechanics simulations.
SAR and QSAR in Environmental Research 01/2008; 19(1-2):179-89. · 1.67 Impact Factor
[show abstract][hide abstract] ABSTRACT: We discuss molecular dynamics simulations for several types of polymeric liquid crystals. Dendrimers with a variety of mesogenic attachments are studied in isotropic, nematic and smectic A solvents, with an emphasize on the coupling between molecular shape and the structure of the phase. The structure and dynamics of liquid crystal side-chain polymers are studied within different bulk phases. Here, again a strong coupling is noted between molecular shape and molecular organisation within each phase. We also consider photo-induced deformation in azobenzene-containing polymers and demonstrate that the “opposite sign” of these deformations, observed experimentally in liquid crystalline and amorphous systems, can be explained solely by the reorientation of trans-isomers of azobenzene.
[show abstract][hide abstract] ABSTRACT: The phase behaviour of three soft core spherocylinder models is investigated with a view to producing an effective potential for use in coarse-grained simulations of liquid crystal phases and polymers composed of rigid and flexible segments. Provided potentials are not made too soft, two of the soft core models are found to work well in terms of successfully reproducing mesophases and in providing considerable improvements in computational speed over other commonly used coarse-grained models. In Monte Carlo simulations a soft-core spherocylinder model in which a cut and shifted Lennard Jones potential is truncated with a linear tangential potential is found to be particularly effective; while for molecular dynamics a better model is provided by a DPD-like quadratic potential. Here, computational speed-ups of 20 30× are seen in equilibration times in comparison to the well-known soft repulsive spherocylinder (SRS) model. The quadratic potential is used in an additional set of coarse-grained simulations of a liquid crystal with a flexible chain, which exhibits spontaneous formation of a nematic phase. The use of different types of interaction sites is also illustrated by the simulation of a spherocylinder with two ``tails'' formed from spheres. Here, varying the hardness of the sphere-spherocylinder interaction potential allows the formation of a smectic-A phase which exhibits microphase separation.
[show abstract][hide abstract] ABSTRACT: Spin-labeled stearic acid species are commonly used for electron paramagnetic resonance (EPR) studies of cell membranes to investigate phase transitions, fluidity, and other physical properties. In this paper, we use large-scale molecular dynamics simulations to investigate the position and behavior of nitroxide spin labels attached to stearic acid molecules in dipalmitoylphosphatidylcholine (DPPC) bilayers. The results of these studies are potentially very important for the interpretation of EPR spectra, which rely on assumptions about the position of the label in the membrane. Additionally, we investigate the effect of chirality and ionization of the carboxyl group of the label. For a non-ionized species, we observe that spin-label molecules are even able to make flip-flop transitions between the leaflets of the bilayer. Such transitions have been previously observed only in very rare cases in molecular simulations.
The Journal of Physical Chemistry B 12/2007; 111(43):12447-53. · 3.61 Impact Factor
[show abstract][hide abstract] ABSTRACT: The choice of lateral and terminal substitution can have a major influence on the structure of a liquid crystalline supermolecule, which in turn can induce radically different phase behaviour. In this study we use molecular dynamics simulations to investigate the shape of a liquid crystal dendrimer within a liquid crystalline solvent. A coarse‐grained (CG) simulation model is employed to represent a third generation dendrimer in which 32 mesogenic groups are bonded to chains at the end of each branch of the dendrimer. In this CG‐model the liquid crystal groups can be appended either terminally or laterally. This bonding option is used to generate the structure of four separate systems: (a) a dendrimer with 32 terminal mesogens, (b) a dendrimer with 32 laterally appended mesogens, (c) and (d) dendrimers with 16 lateral and 16 terminal groups represented with laterally bonded sites on one side of the molecule, model (c) or next to terminally bonded sites, model (d). The simulations show that the dendrimer is able to change shape in response to molecular environment and that the molecular shape adopted depends critically on the nature of the lateral/terminal susbstitution.
[show abstract][hide abstract] ABSTRACT: This article describes some of the progress made towards the simulation of liquid crystalline polymers and dendrimers within
our laboratory. We describe the use of hybrid models, where a mixture of spherical and nonspherical potentials can be linked
together to form model macromolecules. Results are presented for hybrid models of a side-chain and a main chain liquid crystal
polymer, which have been studied by molecular dynamics simulation. Preliminary results are also presented from a modelling
study of a third generation carbosilane liquid crystalline den-drimer. These involve molecular dynamics studies of single
molecules in a solvent using a hybrid Gay-Berne/Lennard-Jones model; and studies of the bulk phases of the dendrimer using
a coarse-grained hybrid spherocylinder/Lennard-Jones model. We also review briefly some of the progress made with other models
for liquid crystals and polymers, point to the problems still faced and some of the current developments designed to overcome
[show abstract][hide abstract] ABSTRACT: Coarse-grained simulations are described in which the behaviour of a system of model liquid crystalline dendrimer molecules is studied in both liquid and smectic-A liquid crystalline phases. The model system is based on a third generation carbosilane dendrimer, which is functionalised at the surface by short polymeric chains terminated in mesogenic units. The design of the coarse-grained model is based on initial Monte Carlo studies of a single carbosilane molecule at an atomistic level, which yield structural data. The coarse-grained dendrimer is represented in terms of a combination of spherical sites representing the dendrimer core and polymer chains, and spherocylinders representing the mesogenic groups. A strong coupling is seen between internal molecular structure and molecular environment, with individual dendrimer molecules undergoing a remarkable transition from spherical to rod-shaped at the isotropic–smectic phase transition. The driving force for mesophase formation is provided by nanoscale microphase separation of mesogens and the dendrimer core.
[show abstract][hide abstract] ABSTRACT: A detailed molecular dynamics simulation study is described for a polysiloxane side chain liquid crystal polymer (SCLCP). The simulations use a coarse-grained model composed of a combination of isotropic and anisotropic interaction sites. On cooling from a fully isotropic polymer melt, we see spontaneous microphase separation into polymer-rich and mesogen-rich regions. Upon application of a small aligning potential during cooling, the structures that form on microphase separation anneal to produce a smectic-A phase in which the polymer backbone is largely confined between the smectic layers. Several independent quenches from the melt are described that vary in the strength of the aligning potential and the degree of cooling. In each quench, defects were found where the backbone chains hop from one backbone-rich region to the next by tunneling through the mesogenic layers. As expected, the number of such defects is found to depend strongly on the rate of cooling. In the vicinity of such a defect, the smectic-A structure of the mesogen-rich layers is disrupted to give nematiclike ordering. Additionally, several extensive annealing runs of approximately 40 ns duration have been carried out at the point of microphase separation. During annealing the polymer backbone is seen to be slowly excluded from the mesogenic layers and lie perpendicular to the smectic-A director. These observations agree with previous assumptions about the structure of a SCLCP and with interpretations of x-ray diffraction and small angle neutron scattering data. The flexible alkyl spacers, which link the backbone to the mesogens, are found to form sublayers around the backbone layer.
The Journal of Chemical Physics 08/2005; 123(3):34908. · 3.16 Impact Factor
[show abstract][hide abstract] ABSTRACT: We report the initial findings of 100 ns molecular dynamics simulations of the role of cellular membranes in general anaesthesia. The effect of xenon on hydrated dipalmitoylphosphatidylcholine bilayers is described. The xenon atoms were found to prefer the interfacial and central regions of the bilayer. The presence of xenon was observed to lead to a small increase in the surface area, membrane thickness, and order of the acyl chains.
[show abstract][hide abstract] ABSTRACT: The crystal structures of several para-substituted ethynylbenzene derivatives; namely, 4-ethynylanisole (1), 4-ethynylmethylbenzoate (2), 4-ethynylbenzaldehyde (3), 4-ethynyl-2,3,5,6-tetrafluoroanisole (4), 4-ethynylthioanisole (5), and 4-ethynyltoluene (6) have been solved from X-ray diffraction data. In 1–4, the molecular packing consists of infinite chains of molecules, linked by intermolecular C–HO hydrogen bonds. The structure of 5 contains weak bifurcated C–HS and C–Hπ
(CC) interactions and that of 6, C–Hπ(benzene) interactions.
[show abstract][hide abstract] ABSTRACT: A series of 1,4-diethynylbenzene (1) derivatives, H–CC–R–CC–H with R=C6H3NH2
(2), C6H3F (3), C6H2F2-2,5 (4), C6F4
(5), C6H2(OCH3)2-2,5 (6) and C6H2(OnC8H17)2-2,5 (7) has been synthesised and their crystal structures determined by single crystal (2–5) or powder (6, 7) X-ray diffraction. The CCHπCC hydrogen bonds dominating structure 1 are gradually replaced by CC–HF ones with the increase of fluorination (3→5), or completely replaced by CCHN and NHπCC bonds in 2, and CCHO in 6 and 7. The related platinum-based polymers, trans-[–Pt(PnBu3)2–CC–R–CC–]n
(R=as above and C6H4,) have been prepared and characterised by spectroscopic methods and thermogravimetry, which show that the amino- and methoxy-derivatives have lowest thermal stability while the fluorinated ones exhibit increasing thermal stability with increasing fluorination. Optical spectroscopic measurements reveal that substituents on the aromatic spacer group do not create strong donor–acceptor interactions along the rigid backbone of the organometallic polymers.
New Journal of Chemistry 01/2003; · 2.97 Impact Factor
[show abstract][hide abstract] ABSTRACT: Molecular dynamics simulations have been carried out to study the structure of a model liquid crystalline dendrimer (LCDr) in solution. A simplified model is used for a third generation carbosilane LCDr in which united atom Lennard-Jones sites are used to represent all heavy atoms in the dendrimer with the exception of the terminal mesogenic groups, which are represented by Gay-Berne potentials. The model dendrimer is immersed in a mesogenic solvent composed of Gay-Berne particles, which can form nematic and smectic-A phases in addition to the isotropic liquid. Markedly different behavior results from simulations in the different phases, with the dendrimer changing shape from spherical to rodlike in moving from isotropic to nematic solvents. In the smectic-A phase the terminal mesogenic units are able to occupy five separate smectic layers. The change in structure of the dendrimer is mediated by conformational changes in the flexible chains, which link the terminal mesogenic moieties to the dendrimer core.
The Journal of Chemical Physics 01/2003; · 3.16 Impact Factor
[show abstract][hide abstract] ABSTRACT: A series of 1:1 complexes of hexafluorobenzene (HFB) with naphthalene, anthracene, phenanthrene, pyrene and triphenylene were prepared and their X-ray crystal structures determined at low temperatures. Each structure contains infinite mixed stacks of alternating nearly-parallel molecules of HFB and arene, which display various slip distortions and form different 3-dimensional motifs. The naphthalene, anthracene and pyrene complexes show polymorphism. Crystal packing of HFB complexes is compared with that of corresponding octafluoronaphthalene complexes. Ab initio DFT calculations on the infinite lattices give lattice parameters and slip parameters in close agreement with the experimental crystal structures, while showing that intermolecular cohesion is predominantly of electrostatic, rather than van der Waals, origin.
New Journal of Chemistry 11/2002; · 2.97 Impact Factor
[show abstract][hide abstract] ABSTRACT: Molecular complexes of 1:1 stoichiometry of octafluoronaphthalene (OFN) with the polyaromatic hydrocarbons anthracene, phenanthrene, pyrene and triphenylene have been prepared, and their single-crystal X-ray structures determined at 120 K. All of the structures are composed of infinite stacks of alternating, almost parallel molecules of OFN and the hydrocarbons, in contrast to the herringbone or c-type (flattened herringbone) packing of the pure components. It is clearly shown that the stacking motif does not require a close correlation between the molecular geometry of the arene and perfluoroarene species, but is stable over a wide range of differing sizes and shapes. Thus, the arene-perfluoroarene interaction is of general importance as a supramolecular synthon. The molecular geometries of the components are not affected by complexation, indicating the absence of charge transfer in the complexes. The role of close C-H . . .F-C and C-F . . .F-C intermolecular contacts between stacks is discussed. A re-determination of the single-crystal structure of triphenylene at 150 K is also reported, providing a more accurate comparison with that of the 1:1 OFN . triphenylene complex.