Electroporation is the formation of permeabilizing structures in the cell membrane under the influence of an externally imposed electric field. The resulting increased permeability of the membrane enables a wide range of biological applications, including the delivery of normally excluded substances into cells. While electroporation is used extensively in biology, biotechnology, and medicine, its molecular mechanism is not well understood. This lack of knowledge limits the ability to control and fine-tune the process. In this article we propose a novel molecular mechanism for the electroporation of a lipid bilayer based on energetics analysis. Using molecular dynamics simulations we demonstrate that pore formation is driven by the reorganization of the interfacial water molecules. Our energetics analysis and comparisons of simulations with and without the lipid bilayer show that the process of poration is driven by field-induced reorganization of water dipoles at the water-lipid or water-vacuum interfaces into more energetically favorable configurations, with their molecular dipoles oriented in the external field. Although the contributing role of water in electroporation has been noted previously, here we propose that interfacial water molecules are the main players in the process, its initiators and drivers. The role of the lipid layer, to a first-order approximation, is then reduced to a relatively passive barrier. This new view of electroporation simplifies the study of the problem, and opens up new opportunities in both theoretical modeling of the process and experimental research to better control or to use it in new, innovative ways.

We present a comprehensive classical molecular dynamics study of water nanodroplets under the influence of an externally applied electric field. Our simulations cover a wide range of droplet sizes and electric field strengths, which allows for a thorough exploration of the structural and energetic behavior of nanodroplets in the presence of an external electric field. Our analysis reveals the molecular-level mechanism behind the shape extension of a nanodroplet from a spheroid to a highly prolate ellipsoid as the propensity of the water dipoles to align with the electric field while simultaneously restructuring to minimize the dipole–dipole interaction energy. We also develop a quantitative theory that describes the energetic landscape for the nanodroplet shape extension process and allows predictions of the nanodroplet behavior based on its initial size and the strength of the applied field.

Molecular dynamics (MD) simulations have long had an important role in the study of equilibrium and nonequilibrium phase transitions. However, the effects of finite system sizes and periodic boundary conditions on such simulation are still not fully understood. In the present paper, we investigate this issue using simulations of the homogeneous melting of superheated crystals, specifically the effect of system size on the delay time before melting (which we call "melting time"). Because melting is a random and relatively rare event, we perform a systematic and extensive MD simulation study of a simple molecular system, solidphase argon in a perfect fcc crystal superheated above the melting point. Using extensive replicate simulations, we first confirm that the distribution of melting times is accurately characterized by a gamma distribution. Next, we use the model of melting being triggered by random dislocations to derive an equation for the mean melting time as a function of system size and show that this model wellmatches our MD data over a range of periodic boxes containing from 256 to 296,352 argon atoms. This equation shows that the system-size effect is inversely proportional to the number of atoms (or equivalently, proportional to L −3 with L being the side length of the periodic box) and could be used as a correction factor for melting times calculated in finite systems. We also study the effects of temperature on melting and find that the mean melting time exponentially decreases to a nonzero asymptotic value with increasing temperature. We observe that the melting time distributions shift toward more Gaussian-like forms of the gamma distribution (i.e., with larger values of the shape parameter) at elevated temperatures. Finally, we also present the results of the melting of water ice I h to show that our findings apply to molecules and melting processes more complex than simple Lennard-Jones systems.

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For computational studies of materials in a realistic manner, appropriate treatment of the Coulombic interaction is critical. Since the potential function is long-range and has both positive and negative signatures, it is not simple to handle the interaction in an effective manner, i.e., with high accuracy, low computational cost, freedom from artifacts, and ease of implementation. We introduce a novel idea, zero-dipole summation, for evaluating the electrostatic energy of classical particle system. The summation prevents the nonzerocharge and nonzero-dipole states artificially generated by simple cutoff truncation, which causes energetic noise and several artifacts. The currently derived energy formula nevertheless takes a simple pairwise form, which utilizes the cutoff procedure but employs a pairwise function changed from the pure Coulomb formula into a new formula taking account of the neutrality of charges and dipoles in the cutoff sphere (Fukuda et al. (2011) J. Chem. Phys. 134, 164107). This simple pairwise form enables us to effectively apply the scheme to high-performance computation. We discuss the theoretical details of our method and investigate the accuracy, stability, and static and dielectric properties of molecular systems via molecular dynamics simulation. We obtained the electrostatic energy error to be 0.01% at practical cutoff distance for an ionic system and a water system. We estimated the radial distribution function and the distant dependent Kirkwood factor for the water system, and confirmed the agreement with those by the Ewald method. Since the Kirkwood factor is very sensitive to the treatment of the electrostatic interaction, the agreement suggests that our method should be distinguishable from many other cutofflike methods, which often cause the significant disagreement. Accurate electrostatic energies were also calculated with our method for a membrane protein with explicit ions and membrane and water molecules. . Molecular electric fields and potentials govern the chemical and physical behavior of molecules. In many biological systems, processes involving charge separation and transport such as enzymatic activity [1, 2], photosynthesis [3] and the electrostatic steering of ligands towards active sites, have been attributed to these fields. Gaining a detailed, quantitative description of the effects molecular electric fields play, will provide for a more precise mechanistic understanding of such chemical phenomena. Until now, obtaining information concerning these fields and potentials from experiments has been a problematic task. It is the principle objective of this investigation to quantitatively determine and describe the molecular electric fields at the oxygen binding site in the heme proteins myoglobin and hemoglobin. By utilizing single molecule and hole-burning spectroscopies, Stark effect measurements will be employed; to study the impact internal electric field distributions play. To this end, we have developed and constructed a cryogenic temperature version of a confoc...