Fabricating a low-temperature synthesized graphene-cellulose acetate-sodium alginate scaffold for the generation of ovarian cancer spheriod and its drug assessment.

3D cell culture can mimic tumor pathophysiology, which reflects cellular morphology and heterogeneity, strongly influencing gene expression, cell behavior, and intracellular signaling. It supports cell-cell and cell-matrix interaction, cell attachment, and proliferation, resulting in rapid and reliable drug screening models. We have generated an ovarian cancer spheroid in interconnected porous scaffolds.

Computing Potential of the Mean Force Profiles for Ion Permeation Through Channelrhodopsin Chimera, C1C2.

Umbrella sampling, coupled with a weighted histogram analysis method (US-WHAM), can be used to construct potentials of mean force (PMFs) for studying the complex ion permeation pathways of membrane transport proteins. Despite the widespread use of US-WHAM, obtaining a physically meaningful PMF can be challenging. Here, we provide a protocol to resolve that issue.

Hydration Mimicry by Membrane Ion Channels.

Ions transiting biomembranes might pass readily from water through ion-specific membrane proteins if these protein channels provide environments similar to the aqueous solution hydration environment. Indeed, bulk aqueous solution is an important reference condition for the ion permeation process. Assessment of this hydration mimicry concept depends on understanding the hydration structure and free energies of metal ions in water in order to provide a comparison for the membrane channel environment.

Probing Translocation in Mutants of the Anthrax Channel: Atomically Detailed Simulations with Milestoning.

Anthrax toxin consists of a cation channel and two protein factors. Translocation of the anthrax protein factors from endosomal to the cytosolic compartment is a complex process which utilizes the cation channel. An atomically detailed understanding of the function of the anthrax translocation machinery is incomplete.

Molecular Dynamics of Lithium Ion Transport in a Model Solid Electrolyte Interphase.

Li transport within a solid electrolyte interphase (SEI) in lithium ion batteries has challenged molecular dynamics (MD) studies due to limited compositional control of that layer. In recent years, experiments and ab initio simulations have identified dilithium ethylene dicarbonate (LiEDC) as the dominant component of SEI layers. Here, we adopt a parameterized, non-polarizable MD force field for LiEDC to study transport characteristics of Li in this model SEI layer at moderate temperatures over long times.

Strontium and barium in aqueous solution and a potassium channel binding site.

Ion hydration structure and free energy establish criteria for understanding selective ion binding in potassium (K) ion channels and may be significant to understanding blocking mechanisms as well. Recently, we investigated the hydration properties of Ba, the most potent blocker of K channels among the simple metal ions. Here, we use a similar method of combining ab initio molecular dynamics simulations, statistical mechanical theory, and electronic structure calculations to probe the fundamental hydration properties of Sr, which does not block bacterial K channels.

Role of Solute Attractive Forces in the Atomic-Scale Theory of Hydrophobic Effects.

The role that van der Waals (vdW) attractive forces play in the hydration and association of atomic hydrophobic solutes such as argon (Ar) in water is reanalyzed using the local molecular field (LMF) theory of those interactions. In this problem, solute vdW attractive forces can reduce or mask hydrophobic interactions as measured by contact peak heights of the ArAr correlation function compared to reference results for purely repulsive core solutes. Nevertheless, both systems exhibit a characteristic hydrophobic inverse temperature behavior in which hydrophobic association becomes stronger with increasing temperature through a moderate temperature range.

Molecular Simulation Results on Charged Carbon Nanotube Forest-Based Supercapacitors.

Electrochemical double-layer capacitances of charged carbon nanotube (CNT) forests with tetraethyl ammonium tetrafluoro borate electrolyte in propylene carbonate are studied on the basis of molecular dynamics simulation. Direct molecular simulation of the filling of pore spaces of the forest is feasible even with realistic, small CNT spacings. The numerical solution of the Poisson equation based on the extracted average charge densities then yields a regular experimental dependence on the width of the pore spaces, in contrast to the anomalous pattern observed in experiments on other carbon materials and also in simulations on planar slot-like pores.

Nanoporous Hydrogels for the Observation of Anthrax Exotoxin Translocation Dynamics.

The ability to observe lethal anthrax exotoxins translocating through size-constricting nanopores in vitro, combined with detailed sequence and structural data, has aided in elucidated mechanisms of exotoxin cell entry and toxicity. However, due to limited observations of anthrax exotoxins translocating through protective antigen nanopores in vitro and the instability of protective antigen-functionalized suspended lipid bilayers, questions remain regarding the native mechanisms of cell entry. Nanoporous hydrogel membranes offer a robust tool for studying protein translocation with ensemble measurements that complement conventional single-molecule translocation measurements.

Assessment of Simple Models for Molecular Simulation of Ethylene Carbonate and Propylene Carbonate as Solvents for Electrolyte Solutions.

Progress in understanding liquid ethylene carbonate (EC) and propylene carbonate (PC) on the basis of molecular simulation, emphasizing simple models of interatomic forces, is reviewed. Results on the bulk liquids are examined from the perspective of anticipated applications to materials for electrical energy storage devices. Preliminary results on electrochemical double-layer capacitors based on carbon nanotube forests and on model solid-electrolyte interphase (SEI) layers of lithium ion batteries are considered as examples.

Quasi-chemical theory of F(aq): The "no split occupancies rule" revisited.

We use ab initio molecular dynamics (AIMD) calculations and quasi-chemical theory (QCT) to study the inner-shell structure of F(aq) and to evaluate that single-ion free energy under standard conditions. Following the "no split occupancies" rule, QCT calculations yield a free energy value of -101 kcal/mol under these conditions, in encouraging agreement with tabulated values (-111 kcal/mol). The AIMD calculations served only to guide the definition of an effective inner-shell constraint.

The Impact of Protonation on Early Translocation of Anthrax Lethal Factor: Kinetics from Molecular Dynamics Simulations and Milestoning Theory.

We report atomically detailed molecular dynamics simulations of the permeation of the lethal factor (LF) N-terminal segment through the anthrax channel. The N-terminal chain is unstructured and leads the permeation process for the LF protein. The simulations were conducted in explicit solvent with milestoning theory, making it possible to extract kinetic information from nanosecond to millisecond time scales.

Scaling Atomic Partial Charges of Carbonate Solvents for Lithium Ion Solvation and Diffusion.

Lithium-ion solvation and diffusion properties in ethylene carbonate (EC) and propylene carbonate (PC) were studied by molecular simulation, experiments, and electronic structure calculations. Studies carried out in water provide a reference for interpretation. Classical molecular dynamics simulation results are compared to ab initio molecular dynamics to assess nonpolarizable force field parameters for solvation structure of the carbonate solvents.

Statistical Analyses of Hydrophobic Interactions: A Mini-Review.

This review focuses on the striking recent progress in solving for hydrophobic interactions between small inert molecules. We discuss several new understandings. First, the inverse temperature phenomenology of hydrophobic interactions, i.

Molecular Theory and the Effects of Solute Attractive Forces on Hydrophobic Interactions.

The role of solute attractive forces on hydrophobic interactions is studied by coordinated development of theory and simulation results for Ar atoms in water. We present a concise derivation of the local molecular field (LMF) theory for the effects of solute attractive forces on hydrophobic interactions, a derivation that clarifies the close relation of LMF theory to the EXP approximation applied to this problem long ago. The simulation results show that change from purely repulsive atomic solute interactions to include realistic attractive interactions diminishes the strength of hydrophobic bonds.

Dielectric Relaxation of Ethylene Carbonate and Propylene Carbonate from Molecular Dynamics Simulations.

Ethylene carbonate (EC) and propylene carbonate (PC) are widely used solvents in lithium (Li)-ion batteries and supercapacitors. Ion dissolution and diffusion in those media are correlated with solvent dielectric responses. Here, we use all-atom molecular dynamics simulations of the pure solvents to calculate dielectric constants and relaxation times, and molecular mobilities.

Octa-Coordination and the Aqueous Ba(2+) Ion.

The hydration structure of Ba(2+) ion is important for understanding blocking mechanisms in potassium ion channels. Here, we combine statistical mechanical theory, ab initio molecular dynamics simulations, and electronic structure methods to calculate the hydration free energy and local hydration structure of Ba(2+)(aq). The predicted hydration free energy (-304 ± 1 kcal/mol) agrees with the experimental value (-303 kcal/mol) when a maximally occupied, unimodal inner solvation shell is treated.

Hydration of Kr(aq) in Dilute and Concentrated Solutions.

Molecular dynamics simulations of water with both multi-Kr and single Kr atomic solutes are carried out to implement quasi-chemical theory evaluation of the hydration free energy of Kr(aq). This approach obtains free energy differences reflecting Kr-Kr interactions at higher concentrations. Those differences are negative changes in hydration free energies with increasing concentrations at constant pressure.

Molecular-scale hydrophobic interactions between hard-sphere reference solutes are attractive and endothermic.

The osmotic second virial coefficients, B2, for atomic-sized hard spheres in water are attractive (B2 < 0) and become more attractive with increasing temperature (ΔB2/ΔT < 0) in the temperature range 300 K ≤ T ≤ 360 K. Thus, these hydrophobic interactions are attractive and endothermic at moderate temperatures. Hydrophobic interactions between atomic-sized hard spheres in water are more attractive than predicted by the available statistical mechanical theory.

Interfaces of propylene carbonate.

Propylene carbonate (PC) wets graphite with a contact angle of 31° at ambient conditions. Molecular dynamics simulations agree with this contact angle after 40% reduction of the strength of graphite-C atom Lennard-Jones interactions with the solvent, relative to the models used initially. A simulated nano-scale PC droplet on graphite displays a pronounced layering tendency and an Aztex pyramid structure for the droplet.

Communication: Direct observation of a hydrophobic bond in loop closure of a capped (-OCH2CH2-)n oligomer in water.

The small r variation of the probability density P(r) for end-to-end separations of a -CH(2)CH(3) capped (-OCH(2)CH(2)-)(n) oligomer in water is computed to be closely similar to the CH(4)···CH(4) potential of mean force under the same circumstances. Since the aqueous solution CH(4)···CH(4) potential of mean force is the natural physical definition of a primitive hydrophobic bond, the present result identifies an experimentally accessible circumstance for direct observation of a hydrophobic bond which has not been observed previously because of the low solubility of CH(4) in water. The physical picture is that the soluble chain molecules carry the capping groups into aqueous solution, and permits them to find one another with reasonable frequency.