The effects of membrane curvature on the free energy barrier for membrane fusion have been investigated using coarse-grained molecular dynamics (CG-MD) simulations, assuming that fusion takes place through a stalk intermediate. Free energy barriers were estimated for stalk formation as well as for fusion pore formation using the guiding potential method. Specifically, the three different geometries of two apposed membranes were considered: vesicle-vesicle, vesicle-planar, and planar-planar membranes. The free energy barriers for the resulting fusion were found to depend importantly on the fusing membrane geometries; the lowest barrier was obtained for vesicular membranes. Further, lipid sorting was observed in fusion of the mixed membranes of dimyristoyl phosphatidylcholine and dioleoyl phosphatidylethanolamine (DOPE). Specifically, DOPE molecules were found to assemble around the stalk to support the highly negative curved membrane surface. A consistent result for lipid sorting was observed when a simple continuum model (CM) was used, where the Helfrich energy and mixing entropy of the lipids were taken into account. However, the CM predicts a much higher free energy barrier than found using CG-MD. This discrepancy originates from the conformational changes of lipids, which were not considered in the CM. The results of the CG-MD simulations reveal that a large conformational change in the lipid takes place around the stalk region, which results in a reduction of free energy barriers along the stalk mechanism of membrane fusion.

The free energy profile of the stalk model of membrane fusion has been calculated using coarse-grained molecular dynamics simulations. The proposed method guides the lipid configuration using a guiding wall potential to make the transition from two apposed membranes to a stalk and a fusion pore. The free energy profile is obtained with a thermodynamic integration scheme using the mean force working on the guiding wall as a response of the system. We applied the method to two apposed flat bilayers composed of dioleoyl phosphatidylethanolamine/dioleoyl phosphatidylcholine expanding over the simulation box under the periodic boundary conditions. The two transition states are identified as pre-stalk and pre-pore states. The free energy barrier for the latter is confirmed to be in good agreement with that estimated by the pulling method. The present method provides a practical way to calculate the free energy profile along the stalk mechanism.

A coarse-grained (CG) model for peptides and proteins was developed as an extension of the Surface Property fItting Coarse grAined (SPICA) force field (FF). The model was designed to examine membrane proteins that are fully compatible with the lipid membranes of the SPICA FF. A preliminary version of this protein model was created using thermodynamic properties, including the surface tension and density in the SPICA (formerly called SDK) FF. In this study, we improved the CG protein model to facilitate molecular dynamics (MD) simulations with a reproduction of multiple properties from both experiments and all-atom (AA) simulations. An elastic network model was adopted to maintain the secondary structure within a single chain. The side-chain analogues reproduced the transfer free energy profiles across the lipid membrane and demonstrated reasonable association free energy (potential of mean force) in water compared to those from AA MD. A series of peptides/proteins adsorbed onto or penetrated into the membrane simulated by the CG MD correctly predicted the penetration depths and tilt angles of peripheral and transmembrane peptides/proteins as comparable to those in the orientations of proteins in membranes (OPM) database. In addition, the dimerization free energies of several transmembrane helices within a lipid bilayer were comparable to those from experimental estimation. Application studies on a series of membrane protein assemblies, scramblases, and poliovirus capsids demonstrated the good performance of the SPICA FF.

Arginine-rich peptide and Antennapedia are cell-penetrating peptides (CPPs) which have the ability to permeate plasma membrane. Deformation of the plasma membrane with CPPs is the key to understand permeation mechanism. We investigate the dynamics of CPP and the lipid bilayer membrane by coarse-grained simulation. We found that the peptide makes inverted micelle in the lipid bilayer membrane, when the attractive potential between the peptide and lipid heads is strong. The inverted micelle is formed to minimize potential energy of the peptide. For vesicle membrane, the peptide moves from the outer vesicle to the inner vesicle through the membrane. The translocation of the peptide suggests inverted micelle model as a possible mechanism of CPPs.

Seeking a new substrate for fabrication of silicene is of high importance, since its formation in experiment is extremely difficult and only a few substrates have been found to be suitable so far. Reporting of other possible substrates for silicene, particularly cheaper alternatives, would also open up the possibility of controlled experimental growth and functionalization of this new nanomaterial. Here, we show, based on first-principles molecular dynamics calculations, that the honeycomb silicene monolayer is stable on the 4 × 4 Al( 111) surface and that it possesses a binding energy comparable to that on the 4 × 4 Ag(111) surface. It is furthermore demonstrated that a new ordered silicene monolayer structure consisting of 3-, 4-, 5-, and 6-sided polygons can also be formed on the Al(111) surface. This new silicene monolayer, which we call "polygonal silicene", possesses an almost flat monolayer structure and exhibits a free electron-like density of state, indicating high electronic conduction. The present findings indicate that silicene can take monolayer forms other than the honeycomb lattice as a result of varying the substrate. Silicene is thus expected to exhibit variable electronic properties, which would extend its applicability to possible future nanoelectronics.