Wataru Shinoda

Large-scale molecular dynamics simulations of self-assembling systems.

Relentless increases in the size and performance of multiprocessor computers, coupled with new algorithms and methods, have led to novel applications of simulations across chemistry. This Perspective focuses on the use of classical molecular dynamics and so-called coarse-grain models to explore phenomena involving self-assembly in complex fluids and biological systems.

Multi-property fitting and parameterization of a coarse grained model for aqueous surfactants

A new systematic approach to build coarse-grained (CG) molecular models for surfactants/water systems is proposed. A step-by-step approach using several molecular systems for the parameterization makes the CG model versatile and transferable. The intramolecular bond potentials are determined to reproduce the bond and angle distributions obtained from all-atom (AA) molecular dynamics (MD) simulations. A careful choice of the potential function for nonbonded interactions is essential for better structural properties. Density and surface/interfacial tension data are used for parameter fitting, because these thermodynamic properties are of key importance in characterizing the self-organized surfactant structure. Solvation (hydration) and transfer free energies, which play an essential role in determining the partition of solute molecules, are also taken into account in the model.

Zwitterionic Lipid Assemblies: Molecular Dynamics Studies of Monolayers, Bilayers, and Vesicles Using a New Coarse Grain Force Field

A new coarse-grained (CG) intermolecular force field is presented for a series of zwitterionic lipids. The model is an extension of our previous work on nonionic surfactants and is designed to reproduce experimental surface/interfacial properties as well as distribution functions from all-atom molecular dynamics (MD) simulations. Using simple functional forms, the force field parameters are optimized for multiple lipid molecules, simultaneously. The resulting CG lipid bilayers have reasonable molecular areas, chain order parameters, and elastic properties. The computed surface pressure vs area (pi-A) curve for a dipalmitoyl phosphatidylcholine (DPPC) monolayer demonstrates a significant improvement over the previous CG models. The DPPC monolayer has a longer persistence length than a polyethyleneglycol (PEG) lipid monolayer, exhibiting a long-lived curved monolayer surface under negative tension. The bud ejected from an oversaturated DPPC monolayer has a large bicelle-like structure, which is different from the micellar bud formed from an oversaturated PEG lipid monolayer. We have successfully observed vesicle formation during CG-MD simulations, starting from an aggregate of dimyristoyl phosphatidylcholine (DMPC) molecules. Depending on the aggregate size, the lipid assembly spontaneously transforms into a closed vesicle or a bicelle. None of the various intermediate structures between these extremes seem to be stable. An attempt to observe fusion of two vesicles through the application of an external adhesion force was not successful. The present CG force field also supports stable multilamellar DMPC vesicles.

Molecular Dynamics Simulations of Ionic Liquids: Cation and Anion Dependence of Self-Diffusion Coefficients of Ions

Molecular dynamics simulations of a series of ionic liquids [1-alkyl-3-methylimidazolium (alkyl = methyl, ethyl, butyl, hexyl, and octyl), 1-butylpyridinium, N-butyl-N,N,N-trimethylammonium and N-butyl-N-methylpyrrolidinium cations combined with a (CF(3)SO(2))(2)N(-) anion ([mmim][TFSA], [emim][TFSA], [bmim][TFSA], [C(6)mim][TFSA], [C(8)mim][TFSA], [bpy][TFSA], [(n-C(4)H(9))(CH(3))(3)N][TFSA], and [bmpro][TFSA]) and a 1-butyl-3-methylimidazolium combined with BF(4)(-), PF(6)(-), CF(3)CO(2)(-), CF(3)SO(3)(-), and (C(2)F(5)SO(2))(2)N(-) anions ([bmim][BF(4)], [bmim][PF(6)], [bmim][CF(3)CO(2)], [bmim][CF(3)SO(3)], and [bmim][BETA])] were carried out using the OPLS force field for ionic liquids. The force field was refined on the basis of ab initio molecular orbital calculations of isolated ions and experimental densities for four ionic liquids. The densities calculated for the 13 ionic liquids agreed with the experimental values within a 2% error. The self-diffusion coefficients calculated for the ions in the 13 ionic liquids were compared with the experimental values obtained by the NMR measurements. Although the calculated self-diffusion coefficients were about 1 order smaller than the experimental ones, the cation and anion dependence (the effects of alkyl chain length in imidazolium, cation structures, and anion species) of the experimental self-diffusion coefficients was reproduced by the simulations quite well in most cases. The translational motion of the terminal carbon atoms in the alkyl chains of the imidazolium cations on the time scale of a few nanoseconds is significantly faster than that of the atoms in the imidazolium rings and anions, which suggests that the dynamics of atoms in the polar domains of the ionic liquids is significantly different from that in the nonpolar domains. The factors determining the self-diffusion coefficients of the ions are also discussed.

Computer simulation studies of self-assembling macromolecules

Coarse-grained (CG) molecular models are now widely used to understand the structure and functionality of macromolecular self-assembling systems. In the last few years, significant efforts have been devoted to construct quantitative CG models based on data from molecular dynamics (MD) simulations with more detailed all-atom (AA) intermolecular force fields as well as experimental thermodynamic data. We review some of the recent progress pertaining to the MD simulation of self-assembling macromolecular systems, using as illustrations the application of CG models to probe surfactant and lipid self-assembly including liposome and dendrimersome formation as well as the interaction of biomembranes with nanoparticles.

Cholesterol effect on water permeability through DPPC and PSM lipid bilayers: a molecular dynamics study.

Water permeability of two different lipid bilayers of dipalmitoylphosphatidylcholine (DPPC) and palmitoylsphingomyelin (PSM) in the absence and presence of cholesterol (0-50 mol %) have been studied by molecular dynamics simulations to elucidate the molecular mechanism of the reduction in water leakage across the membranes by the addition of cholesterol. An enhanced free energy barrier was observed in these membranes with increased cholesterol concentration, and this was explained by the reduced cavity density around the cholesterol in the hydrophobic membrane core. There was an increase of trans conformers in the hydrophobic lipid chains adjacent to the cholesterol, which reduced the cavity density. The enhanced free energy barrier was found to be the main reason to reduce the water permeability with increased cholesterol concentration. At low cholesterol concentrations the PSM bilayer exhibited a higher free energy barrier than the DPPC bilayer for water permeation, while at greater than 30 mol % of cholesterol the difference became minor. This tendency for the PSM and DPPC bilayers to resemble each other at higher cholesterol concentrations was similar to commonly observed trends in several structural properties, such as order parameters, cross-sectional area per molecule, and cavity density profiles in the hydrophobic regions of bilayer membranes. These results demonstrate that DPPC and PSM bilayers with high cholesterol contents possess similar physical properties, which suggests that the solubility of cholesterol in these lipid bilayers has importance for an understanding of multicomponent lipid membranes with cholesterol.

A Voronoi analysis of lipid area fluctuation in a bilayer

Membrane area fluctuation of the lipid bilayer has been investigated based upon two-dimensional Voronoi tessellation analysis for the centers of mass of the lipid molecules projected on the bilayer plane. Long-time trajectories of the molecules used in the analysis have been generated by molecular dynamics calculations. The single-molecular area defined by Voronoi polygon showed a broad Gaussian distribution, from which area distribution of the membrane composed of N lipid molecules may satisfactorily be predicted. The fluctuation was found to be caused mainly by thermal motions of the alkyl chains. The number of gauche conformation and alkyl chain length was strongly correlated to the molecular area. Head group motions, however, showed little contribution to the fluctuation. Geometry of Voronoi polygons and the number of nearest neighbor molecules showed rather broad distribution due to the thermal fluctuation. This is in contrast to the structure found in the ripple, gel, and crystal phases. Formation o...

United-Atom Acyl Chains for CHARMM Phospholipids

In all-atom simulations of lipid membranes, explicit hydrogen atoms contained in the hydrocarbon region are described by a large number of degrees of freedom, although they convey only limited physical information. We propose an implicit-hydrogen model for saturated and monounsaturated acyl chains, aimed at complementing the all-atom CHARMM27 model for phospholipid headgroups. Torsional potentials and nonbonded parameters were fitted to reproduce experimental data and free energy surfaces of all-atom model systems. Comparative simulations of fluid-phase POPC bilayers were performed using the all-hydrogen force field and the present model. The hybrid model accelerates a typical bilayer simulation by about 50% while sacrificing a minimal amount of detail with respect to the fully atomistic description. In addition, the united-atom description is energetically compatible with all-atom CHARMM models, making it suitable for simulations of complex membrane systems.

Molecular dynamics study of a lipid bilayer: Convergence, structure, and long-time dynamics

Long time molecular dynamics simulations for the dipalmitoylphosphatidylcholine lipid bilayer in the liquid crystal phase could successfully be performed in the isothermal-isobaric ensemble using the Nose-Parrinello-Rahman extended system method. Three independent 2 ns calculations show excellent convergence to the same equilibrium state of the system in about 0.5 ns. Various structural properties such as atomic distribution, order parameter, gauche fraction in the alkyl chains, and bent structure of the head group and sn-2chain were satisfactorily reproduced. Dynamic quantities such as trans-gauche transition were qualitatively in good correspondence to the experiment. The calculations presented a microscopic picture of the whole molecular conformations, including the finding that there is not a collective tilt in the bilayer. Some interesting dynamical observations concerning large structural fluctuations and pendulum motion of the alkyl chains were also made.

Free-energy analysis of the molecular binding into lipid membrane with the method of energy representation

A statistical-mechanical treatment of the molecular binding into lipid membrane is presented in combination with molecular simulation. The membrane solution is viewed as an inhomogeneous, mixed solvent system, and the free energy of solvation of a solute in membrane is computed with a realistic set of potential functions by the method of energy representation. Carbon monoxide, carbon dioxide, benzene, and ethylbenzene are adopted as model solutes to analyze the binding into 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine (DMPC) membrane. It is shown that the membrane inside is more favorable than bulk water and that the solute distribution is diffuse throughout the membrane inside. The membrane-water partition coefficient is then constructed with the help of the Kirkwood-Buff theory from the solvation free energy obtained separately in the hydrophobic, glycerol, headgroup, and aqueous regions. To discuss the role of repulsive and attractive interactions, the solvation free energy is partitioned into the DMPC and water contributions and the effect of water to stabilize the benzene and ethylbenzene solutes within the membrane is pointed out.