1. Coarse-Grained Molecular Model
(1) Coarse-Grained Molecular Model based on all atoms (CHARMM)
We are developing a coarse-grained molecular force field for surfactants, lipids, carbon materials, nanoparticles, and peptides using multi-property fitting as well as distribution functions obtained from all atomic molecular dynamics trajectories. For details, please visit the CG webpage.
all-atom and coarse grain description of DMPG bilayer
(2) Bridging to Mesoscopic Continuum Model
By coarse-grained molecular dynamics simulation, it makes possible to calculate the vesicle whichi is a film closed with a larger membrane system and curvature. In the small lipid aggregates, only vesicles in water is not a stable structure, disc-shaped structure called a bi-cell also will appear as a (quasi) stable structure. The free energy calculation between these stable structures has been done. By comparing the results with continuum (elastic body) by phenomenological theory and, we can evaluate the validity of the theoretical model and the applicability in small scale. In addition, we try to extend the theory on the basis of this observation.
Free energy changes of a vesicle to open a mouth; l is the line length of the bilayer edge. A comparison between MD and continuum theory. (J. Chem.Phys. 2013)
2. Self-Assembly of Macromolecules
Complex fluids including amphiphilic macromolecules show rich phase behaviors including micelle, hexagonal, lamellar, cubic, and inverse phases. To exploit such surfactant self-assembly on the molecular level, a coarse-grained molecular dynamics (CG-MD) simulation is quite useful. Our CG model is desined to reproduce the distribution functions from all-atom molecular simulation and the experimental interfacial and thermodynamic properties including surface tension and solvation free energy. We also confirmed reasonble elastic properties of self-assembly such as lipid membranes, which guarantees the quality of the predicted phase behaviour to some extents. We confrimed that our CG model can predict a correct phase behavior for many surfactants and lipids.
Fig. Self-assembled structure of C12E6 at 303K in water (Curr. Opin. Struct. Biol. 2012)
3. Lipid and Biological Membranes
(1) Membrane Morphology
Lipid membranes change its morphology depending on their lipid components, thermodynamic and solution conditions such as temperature, pH, and salt concentration, and also by the addition of proteins, peptides, and nanoparticles interacting with the membranes. We are interested in the molecular process to cause the morphology changes of membranes. Biological membranes are not homogeneous, showing the heterogeneous distribution of lipid components not only bewteen inner and outer leaflets but also in the same leaflet. Many research works have been done on heterogeneous membrane structure in terms of biological functions. We have done a coarse-grained molecular modeling to investigate the membrane morphology including curved membranes such as vesicles using molecular dynamics simulation. In a mixed lipid vesicle, the free energy required for the vesicle deformation is reduced due to the lipid sorting (Pure Appl. Chem. 2014). We are working on the effect of additives (amphiphilic peptides, proteins, nanoparticles) on the free energy barrier for morphology changes.
Lipid distribution in spherical and deformed vesicles made of DMPC and DOPE mixture. (Pure Appl. Chem. 2014)
(2) Membrane Fusion
Membrane fusion is a fundamental biological process occurring in cell membranes. Therefore, the molecular mechanism of the fusion process has been widely investigated. The process should be affected by local lipid components, hydration, electrostatic interaction, proteins interplaying with membranes, and so on. We have developed a coarse-grained molecular model to treat large-scale phenomena such as membrane fusion involving vesicles. We have also proposed a free energy method to evaluate the free energy barrier along the stalk mechanism of the membrane fusion. Using these computational tools, we now try to understand what reduces or increases the free energy barrier of the membrane fusion process quantitatively.
Fig. Simulation of a vesicle interacting with a membrane (Ref: Science, 2008)
(3) Mechanical Properties of Membranes
Lipid membranes are conventionally described by a continuum theory based on the Helfrich Hamiltonian, in which the membrane is treated as an elastic sheet with zero thickness. The sucess of the continuum theory to characterize the membrane physics at the micrometer scale motivated us to compute the elastic constants from molecular dynamics simulations. By having a good estimate of elastic constants from MD, we can predict the mesoscopic elastic behavior of vesicles based on the molecular details. A comparison of MD and experimental results for the elastic properties provides a good examination for the molecular models, too. One of the examples in this kind of research activities is to develop a method of a free energy evaluation of a membrane as a function of imposed curvature. (Figure) Pressure profiles across the membranes are also useful to evaluate the elastic constants and spontaneous curvatures. Now the pressure profile calculation is also applicable to a spherical coordinate, which is useful for spherical vesicles.
Fig. Curved membranes supported by the guiding external potential (black circle). Bending modulus is estimated by the relation between the membrane curvature and the force required to support the membranes. (J. Chem. Phys. 2013)
4. Inonic Liquid
Molecular dynamics simulations have been used to investigate the structural and dynamical properties of ionic liquids. We are particuarlly interested in "solvate" ionic liquids.
Fig. Various structure of Li+-glyme complex observed in an MD simulation