Molecular dynamics simulation of the formation, structure, and dynamics of small phospholipid vesicles

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.     

Molecular dynamics simulations of PAMAM dendrimer-induced pore formation in DPPC bilayers with a coarse-grained model

We have performed 0.5-micros-long molecular dynamics (MD) simulations of 0%, 50%, and 100% acetylated third- (G3) and fifth-generation (G5) polyamidoamine (PAMAM) dendrimers in dipalmitoylphosphatidylcholine (DPPC) bilayers with explicit water using the coarse-grained (CG) model developed by Marrink et al. (J.Phys. Chem. B 2004, 108, 750-760), but with long-range electrostatic interactions included. Radii of gyration of the CG G5 dendrimers are 1.99-2.32 nm, close to those measured in the experiments by Prosa et al. (J. Polym. Sci. 1997, 35, 2913-2924) and atomistic simulations by Lee et al. (J. Phys. Chem. B 2006, 110, 4014-4019). Starting with the dendrimer initially positioned near the bilayer, we find that positively charged un-acetylated G3 and 50%-acetylated and un-acetylated G5 dendrimers insert themselves into the bilayer, and only un-acetylated G5 dendrimer induces hole formation at 310 K, but not at 277 K, which agrees qualitatively with experimental observations of Hong et al. (Bioconj. Chem. 2004, 15, 774-782) and Mecke et al. (Langmuir 2005, 21, 10348-10354). At higher salt concentration (approximately 500 mM NaCl), un-acetylated G5 dendrimer does not insert into the bilayer. The results suggest that with inclusion of long-range electrostatic interactions into coarse-grained models, realistic MD simulation of membrane-disrupting effects of nanoparticles at the microsecond time scale is now possible.     

Molecular dynamics simulation of hydrated DPPC monolayers using charge equilibration force fields

We present results of molecular dynamics simulations of a model DPPC-water monolayer using charge equilibration (CHEQ) force fields, which explicitly account for electronic polarization in a classical treatment of intermolecular interactions. The surface pressure, determined as the difference between the monolayer and pure water surface tensions at 323 K, is predicted to be 22.92 ±1.29 dyne/cm, just slightly below the broad range of experimental values reported for this system. The surface tension for the DPPC-water monolayer is predicted to be 42.35 ±1.16 dyne/cm, in close agreement with the experimentally determined value of 40.9 dyne/cm. This surface tension is also consistent with the value obtained from DPPC monolayer simulations using state-of-the-art nonpolarizable force fields. The current results of simulations predict a monolayer-water potential difference relative to the pure water-air interface of 0.64 ±0.02 Volts, an improved prediction compared to the fixed-charge CHARMM27 force field, yet still overestimating the experimental range of 0.3 to 0.45 Volts. As the charge equilibration model is a purely charge-based model for polarization, the current results suggest that explicitly modeled polarization effects can offer improvements in describing interfacial electrostatics in such systems.     

Density functional simulation of spontaneous formation of vesicle in block copolymer solutions

The author carries out numerical simulations of vesicle formation based on the density functional theory for block copolymer solutions. It is shown by solving the time evolution equations for concentrations that a polymer vesicle is spontaneously formed from the homogeneous state. The vesicle formation mechanism obtained by this simulation agrees with the results of other simulations based on the particle models as well as experiments. By changing parameters such as the volume fraction of polymers or the Flory-Huggins interaction parameter between the hydrophobic subchains and solvents, the spherical micelles, cylindrical micelles, or bilayer structures can also be obtained. The author also shows that the morphological transition dynamics of the micellar structures can be reproduced by controlling the Flory-Huggins interaction parameter.     

Molecular dynamics simulation of cellobiose in water

The conformational behavior of cellobiose was studied by molecular dynamics simulation in a periodic box of waters. Several different initial conformations were used and the results compared with equivalent vacuum simulations. The average positions and rms fluctuations within single torsional conformations of cellobiose were affected only slightly by the solvent. However, water damped local torsional librations and transitions. The conformational energies of the solute and their fluctuations were also sensitive to the presence of solvent. Intramolecular hydrogen bonding was weakened relative to that observed in vacuo due to competition with solvating waters. All cellobiose hydroxyl groups participated in intermolecular hydrogen bonds with water, with approximately eight hydrogen bonds formed per glucose ring. The hydrogen bonding was predominantly between water hydrogens and solute hydroxyl oxygens. Intermolecular hydrogen bonding to ring and bridge oxygens was seldom present. The diffusion coefficients of both water and solute agree closely with experimental values. Water interchanged rapidly between the solvating first shell and the bulk on the picosecond time scale. © 1993 John Wiley & Sons, Inc.     

液态水的分子动力学模拟

用分子动力学(MD)模拟方法在150~376K的温度范围内对液态水的微正则系统进行了研究。考察了液态水的结构及其性质。模拟采用了由从头算得出的柔性水-水相互作用势MCYL。对时间和空间的平均得出了液态中水分子几何构型及温度改变所引起的液态水结构变化。对径向分布函数gOH, gOO, gHH及配位数的分析表明, 在所考察的温度范围内, 每个水分子与相邻分子形成的氢键数为2~3, 水分子在参与的2个氢键中同时作为授受体。结合对振动谱的研究表明在低温时液态水形成的网络结构可能随温度的升高而形成小的簇结构。     

Molecular dynamics simulation of a water/metal interface

First results of a molecular dynamics study of a water/metal interface, lasting 3.3 ps at an average temperature of 294 K, are reported. The basic periodic box contains 216 water molecules and a crystal slab of 550 platinum atoms with (100) surface planes. A combination of a Lennard-Jones potential between centers of mass and a Coulomb potential arising from dielectric interactions of the water charge distribution with the metal is employed for the water-wall interaction, the ST2 model for the water-water, and a nearest-neighbour harmonic potential for the platinum-platinum interactions. Considerable adsorption at the interface together with a drastic change of the water structure is observed.     

Solvation dynamics of DCM in a DPPC vesicle entrapped in a sodium silicate derived sol-gel matrix

Solvation dynamics of 4-(dicyanomethylene)-2-methyl-6(p-dimethylaminostyryl) 4H-pyran (DCM) has been studied in a dipalmitoyl-phosphatidylcholine (DPPC) vesicle entrapped in a sodium silicate derived sol-gel glass. Solvation dynamics in DPPC in a sol-gel glass is described by two components of 350 +/- 50 ps (50%) and 2300 +/- 200 ps (50%) with a total dynamic Stokes shift of 1300 cm(-1). The fast component (350 ps) is similar to the fast component in a DPPC vesicle in bulk water (320 +/- 50 ps). This component may be ascribed to the dynamics of the water molecules inside the water pool of the vesicle. However, the slow component (2300 +/- 200 ps) is about 2.5 times slower compared to the slow component of solvation dynamics of DCM in a DPPC vesicle in bulk solvent (900 +/- 100 ps). The anisotropy decay of DCM in a DPPC vesicle both in sol-gel glass and in bulk water exhibits a very fast initial decay with a large residual anisotropy, which does not decay in approximately 10 ns. The time scale of anisotropy decay is very different from that of solvation dynamics.     

Molecular dynamics simulation of the water|nitrobenzene interface

The structure and dynamics of the neat water|nitrobenzene liquid|liquid interface are studied at 300 K using molecular dynamics computer simulations. The water is modeled using the flexible SPC potential, and the nitrobenzene is modeled using an empirically determined nitrobenzene potential energy function. Although nitrobenzene is a polar liquid with a large dielectric constant, the structure of the interface is similar to other water|non-polar organic liquid interfaces. Among the main structural features we describe are an enhancement of interfacial water hydrogen bonds, the specific orientation of water dipoles and nitrobenzene molecules, and a rough surface that is locally sharp. Surface roughness is also characterized dynamically. The dynamics of molecular reorientation are shown to be only mildly modified at the interface. The effect due to the polarizable many-body potential energy functions of both liquids is investigated and is found to affect only mildly the above results.     

Molecular dynamics simulation of the association of nonpolar spheres in water

We apply molecular dynamics (MD) simulations to the study of the association of nonpolar spheres of effective radii between 1.6 and 6.1 A dissolved in water. The constrained MD method is used to calculate the potential of mean force (PMF) of the interaction between spheres. The depth of the potential of mean force increases with increasing radius of the nonpolar sphere. Our results suggest that the PMF is largely governed by size or entropic effects, and that energetic effects associated with the breaking or distortion of hydrogen bonds are of minor importance.     

Molecular dynamics simulation of the renin inhibitor H142 in water

Summary H142 is a synthetic decapeptide designed to inhibit renin, an enzyme acting in the regulation of blood pressure. The inhibiting effect of H142 is caused by a reduction of a-Leu-Val-peptide bond (i. e. C(=O)-NHCH₂-NH). The conformational and dynamical properties of H142 and its unreduced counterpart (H142n) was modelled by means of molecular dynamics simulations. Water was either included explicitly in the simulations or as a dielectric continuum. When water molecules surround the peptides, they remain in a more or less extended conformation through the simulation. If water is replaced by a dielectric continuum, the peptides undergo a conformational change from an extended to a folded state. It is not clear whether this difference is a consequence of a too short simulation time for the water simulations, a force-field artifact promoting extended conformations, or if the extended conformation represents the true conformational state of the peptide. A number of dynamic properties were evaluated as well, such as overall rotation, translational diffusion, side-chain dynamics and hydrogen bonding.     

Molecular dynamics simulation of the PEO sulfonic acid anion in water

Atomistic molecular modeling has been used to study the sulfonic acid anion of poly(ethylene oxide) (PEO sulfonic acid anion) in vacuum and a polymer electrolyte system consisting of the PEO sulfonic acid anion in water. The vibrational spectra of the molecules were simulated by the local mode method and found to be in good agreement with the experimental IR and Raman spectra. The structure of PEO sulfonic acid anion was studied in vacuum and water and compared to the structure of an isolated PEO sulfonic acid in vacuum. The simulated value for the root mean square end-to-end distance for the PEO sulfonic acid anion was 22 Å in vacuum and 12 Å in water. The root mean square radius of gyration of the PEO sulfonic acid anion was 8.4 Å in vacuum and 5.6 Å in water. The PEO sulfonic acid anion was randomly coiled in water and in an extended shape in vacuum.     

Structured water in polyelectrolyte dendrimers: understanding small angle neutron scattering results through atomistic simulation

Based on atomistic molecular dynamics (MD) simulations, the small angle neutron scattering (SANS) intensity behavior of a single generation-4 polyelectrolyte polyamidoamine starburst dendrimer is investigated at different levels of molecular protonation. The SANS form factor, P(Q), and Debye autocorrelation function, γ(r), are calculated from the equilibrium MD trajectory based on a mathematical approach proposed in this work. The consistency found in comparison against previously published experimental findings (W.-R. Chen, L. Porcar, Y. Liu, P. D. Butler, and L. J. Magid, Macromolecules 40, 5887 (2007)) leads to a link between the neutron scattering experiment and MD computation, and fresh perspectives. The simulations enable scattering calculations of not only the hydrocarbons but also the contribution from the scattering length density fluctuations caused by structured, confined water within the dendrimer. Based on our computational results, we explore the validity of using radius of gyration R(G) for microstructure characterization of a polyelectrolyte dendrimer from the scattering perspective.     

Molecular dynamics simulation of pressure-driven water flow in silicon-carbide nanotubes

Many properties of silicon carbide (SiC) nanotubes, such as their high mechanical strength and resistance to corrosive environments, are superior to those of their carboneous counterparts, namely, carbon nanotubes (CNTs) and, therefore, SiC nanotubes can be a viable alternative to CNTs in a variety of applications. We employ molecular dynamics simulations to examine flow of water in SiC nanotubes and to study the differences and similarities with the same phenomenon in the CNTs. The simulations indicate that SiC nanotubes always provide larger flow enhancements than those reported for the CNTs. Moreover, a given flow enhancement in SiC nanotubes requires an applied pressure gradient that is at least an order of magnitude smaller than the corresponding value in a CNT of the same size.     

Molecular dynamics simulation of liquid water between two walls

A molecular dynamics simulation, lasting ≈25 ps, has been performed with 150 ST2 water molecules between two quasi-hard repulsive walls, at a temperature of 302 K. A number of static and dynamic properties have been computed as a function of the distance from the walls, showing that water near the walls is in general more “ordered” than in the bulk, and that this bulk water behaves like ordinarv liquid ST2 water.     

Molecular dynamics simulation of the coalescence of nanometer-sized water droplets in n-heptane

Molecular dynamics simulations using a modified Drieding 2.21 force field were carried out to study the coalescence behavior of nanometer-sized water droplets in vacuum and in n-heptane. The coalescence mechanisms of the water droplets in the above-noted environments are fairly similar in a sense that the water droplets form a bridge linking the droplets before they merge. However, in the latter situation, due to the presence of n-heptane molecules in between the water droplets, the coalescence was observed to be slowed down considerably, especially in the first 10 ps of the process. However, once the bridge is formed, the water droplets, in both situations, spend about the same amount of time to form a single droplet. The maximum distance between the droplets above which coalescence does not occur was found to be 10 A. In terms of the dynamics, the diffusion coefficient of n-heptane in the emulsion system was very close to its value in the pure liquid form. This may be because n-heptane is the continuous phase. Nonetheless, the dynamic behavior of water in n-heptane is different from that of pure water during and after the coalescence. In particular, the self-diffusion coefficient of water molecules in n-heptane is about 20% higher than the experimental value of pure water. Due to the lack of strong attraction forces between water and n-heptane molecules, the n-heptane molecules were observed to orient themselves perpendicularly to the water/n-heptane interfaces so that the contacting area is minimized.     

Molecular dynamics simulation of sub-and supercritical water with a new interaction potential

A molecular dynamics experiment was performed for water under sub-and supercritical conditions with a new interaction potential including the nonelectrostatic H-bond component. The internal energy, self-diffusion coefficient, mean number of H-bonds per water molecule, and distributions of molecules according to the number of H-bonds were calculated over a wide temperature range at pressures of 50 and 100 MPa. The temperature dependences of these properties were analyzed.     

Molecular dynamics simulations of DiI-C18(3) in a DPPC lipid bilayer

We performed a 40 ns simulation of 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI-C18(3)) in a 1,2-dipalmitoyl-sn-glycero-3-phosphatidyl choline (DPPC) bilayer in order to facilitate interpretation of lipid dynamics and membrane structure from fluorescence lifetime, anisotropy, and fluorescence correlations spectroscopy (FCS). Incorporation of DiI of 1.6 to 3.2 mol% induced negligible changes in area per lipid but detectable increases in bilayer thickness, each of which are indicators of membrane structural perturbation. The DiI chromophore angle was 77 +/- 17 degrees with respect to the bilayer normal, consistent with rotational diffusion inferred from polarization studies. The DiI headgroup was located 0.63 nm below the lipid head group-water interface, a novel result in contrast to some popular cartoon representations of DiI but consistent with DiI's increase in quantum yield when incorporated into lipid bilayers. Importantly, the fast component of rotational anisotropy matched published experimental results demonstrating that sufficient free volume exists at the sub-interfacial region to support fast rotations. Simulations with non-charged DiI head groups exhibited DiI flip-flop, demonstrating that the positively-charged chromophore stabilizes the orientation and location of DiI in a single monolayer. DiI induced detectable changes in interfacial properties of water ordering, electrostatic potential, and changes in P-N vector orientation of DPPC lipids. The diffusion coefficient of DiI (9.7 +/- 0.02 x 10(-8) cm2 s(-1)) was similar to the diffusion of DPPC molecules (10.7 +/- 0.04 x 10(-8) cm2 s(-1)), supporting the conclusion that DiI dynamics reflect lipid dynamics. These results provide the first atomistic level insight into DiI dynamics, results essential in elucidating lipid dynamics through single molecule fluorescence studies.     

Molecular orientational and dipolar correlation in the liquid crystal mixture E7: a molecular dynamics simulation study at a fully atomistic level

Molecular dynamics simulations are reported for the four component nematic liquid crystal mixture E7, which is used commercially. We are able to show the growth of a nematic phase directly from an isotropic liquid over a 100 ns period for an all-atom model, and study orientational and dipole order within the nematic phase. The simulations show that the cyanoterphenyl component of the mixture, 5CT, is more ordered than the three cyanobiphenyl components. The simulations show also that both parallel and anti-parallel dipole correlation take place in E7 but that the strong anti-parallel dipole correlation is localised to particular arrangements of molecules. It is possible to identify two key preferred configurations for molecular pairs in the fluid, which explain the form of the dipole correlation function, g(1)(r).