Various biophysical processes involve the formation of aqueous pores over lipid membranes, including processes of membrane fusion, antimicrobial peptide activity, lipid flip-flop, and membrane permeation. Reliable and efficient free-energy calculations of pore formation using molecular dynamics simulations remained challenging due to the lack of good reaction coordinates (RCs) for pore formation. We present a new RC for pore formation that probes the formation and rupture of a continuous polar defect over the membrane. Potential of mean force (PMF) calculations along the new RC rapidly converge and exhibit no hysteresis between pore-opening and pore-closing pathways, in contrast to calculations based on previous RCs. We show that restraints along the new RC may restrain the system tightly to the transition state of pore formation, rationalizing the absence of hysteresis. We observe that the PMF of pore formation in a tension-free membrane of dimyristoylphosphatidylcholine (DMPC) reveals a free-energy barrier for pore nucleation, confirming a long-hypothesized metastable prepore state. We test the influence of the lipid force field, the cutoff distance used for Lennard-Jones interactions, and the lateral membrane size on the free energies of pore formation. In contrast to PMF calculations based on previous RCs, we find that such parameters have a relatively small influence on the free energies of pore nucleation. However, the metastability of the open pore in DMPC may depend on such parameters. The RC has been implemented into an extension of the GROMACS simulation software. The new RC allows for reliable and computationally efficient free-energy calculations of pore formation in lipid membranes.

Transmembrane pores play an important role in various biophysical processes such as membrane permeation, membrane fusion, and antimicrobial peptide activity. In principal, all-atom molecular dynamics (MD) simulations provide an accurate model of pore formation in lipid membranes. However, the free energy landscape of transmembrane pore formation remains poorly understood, partly because potential of mean force (PMF) calculations of pore formation strongly depend on the choice of the reaction coordinate. In this study, we used umbrella sampling to compute PMFs for pore formation using three different reaction coordinates, namely, (i) a coordinate that steers the lipids in the lateral direction away from the pore center, (ii) the distance of a single lipid phosphate group from the membrane center, and (iii) the average water density inside a membrane-spanning cylinder. Our results show that while the three reaction coordinates efficiently form pores in membranes, they suffer from strong hysteresis between pore-opening and pore-closing simulations, suggesting that they do not restrain the systems close to the transition state for pore formation. The two reaction coordinates that act via restraining the lipids lead to more pronounced hysteresis compared with the coordinate acting on the water molecules. By comparing PMFs computed from membranes with different numbers of lipids, we observed significant artifacts from the periodic boundary conditions in small simulation systems. Further analysis suggests that the formation and disruption of a continuous hydrogen-bonding network across the membrane corresponds to the transition state for pore formation. Our study provides molecular insights into the critical steps of transmembrane pore formation, and it may guide the development of efficient reaction coordinates for pore formation.

The thermal behavior of free and alumina-supported iron-carbon nanoparticles is investigated via molecular dynamics simulations, in which the effect of the substrate is treated with a simple Morse potential fitted to ab initio data. We observe that the presence of the substrate raises the melting temperature of medium and large Fe1−xCx nanoparticles (x = 0 − 0.16, N = 80 − 1000, nonmagic numbers) by 40-60 K; it also plays an important role in defining the ground state of smaller Fe nanoparticles (N = 50 − 80). The main focus of our study is the investigation of Fe-C phase diagrams as a function of the nanoparticle size. We find that as the cluster size decreases in the 1.1-1.6-nm-diameter range the eutectic point shifts significantly not only toward lower temperatures, as expected from the Gibbs-Thomson law, but also toward lower concentrations of C. The strong dependence of the maximum C solubility on the Fe-C cluster size may have important implications for the catalytic growth of carbon nanotubes by chemical vapor deposition.

The formation and closure of aqueous pores in lipid bilayers is a key step in various biophysical processes. Large pores are well described by classical nucleation theory, but the free-energy landscape of small, biologically relevant pores has remained largely unexplored. The existence of small and metastable "prepores" was hypothesized decades ago from electroporation experiments, but resolving metastable prepores from theoretical models remained challenging. Using two complementary methods-atomistic simulations and self-consistent field theory of a minimal lipid model-we determine the parameters for which metastable prepores occur in lipid membranes. Both methods consistently suggest that pore metastability depends on the relative volume ratio between the lipid head group and lipid tails: lipids with a larger head-group volume fraction (or shorter saturated tails) form metastable prepores, whereas lipids with a smaller head-group volume fraction (or longer unsaturated tails) form unstable prepores.

Combining in situ studies of the catalyst activity during single-walled carbon nanotube ͑SWCNT͒ growth by mass spectrometry with differential scanning calorimetry and Raman spectroscopy results, the authors expose the favorable features of small catalyst for SWCNT growth and their relationship with synthesis parameters. The sequential introduction of 12 C and 13 C labeled hydrocarbon reveals the influence of catalyst composition on its lifetime and the growth termination path. Ab initio and molecular dynamics simulations corroborate "V"-shape liquidus line of metal-carbon nanoparticle binary phase diagram, which explains observed carbon-induced solid-liquid-solid phase transitions during nanotube growth.