Ultrasound enhanced diffusion in hydrogels: An experimental and non-equilibrium molecular dynamics study.

Focused ultrasound has experimentally been found to enhance the diffusion of nanoparticles; our aim with this work is to study this effect closer using both experiments and non-equilibrium molecular dynamics. Measurements from single particle tracking of 40 nm polystyrene nanoparticles in an agarose hydrogel with and without focused ultrasound are presented and compared with a previous experimental study using 100 nm polystyrene nanoparticles. In both cases, we observed an increase in the mean square displacement during focused ultrasound treatment. We developed a coarse-grained non-equilibrium molecular dynamics model with an implicit solvent to investigate the increase in the mean square displacement and its frequency and amplitude dependencies. This model consists of polymer fibers and two sizes of nanoparticles, and the effect of the focused ultrasound was modeled as an external oscillating force field. A comparison between the simulation and experimental results shows similar mean square displacement trends, suggesting that the particle velocity is a significant contributor to the observed ultrasound-enhanced mean square displacement. The resulting diffusion coefficients from the model are compared to the diffusion equation for a two-time continuous time random walk. The model is found to have the same frequency dependency. At lower particle velocity amplitude values, the model has a quadratic relation with the particle velocity amplitude as described by the two-time continuous time random walk derived diffusion equation, but at higher amplitudes, the model deviates, and its diffusion coefficient reaches the non-hindered diffusion coefficient. This observation suggests that at higher ultrasound intensities in hydrogels, the non-hindered diffusion coefficient can be used.

Highly parallelizable path sampling with minimal rejections using asynchronous replica exchange and infinite swaps.

Capturing rare yet pivotal events poses a significant challenge for molecular simulations. Path sampling provides a unique approach to tackle this issue without altering the potential energy landscape or dynamics, enabling recovery of both thermodynamic and kinetic information. However, despite its exponential acceleration compared to standard molecular dynamics, generating numerous trajectories can still require a long time. By harnessing our recent algorithmic innovations-particularly subtrajectory moves with high acceptance, coupled with asynchronous replica exchange featuring infinite swaps-we establish a highly parallelizable and rapidly converging path sampling protocol, compatible with diverse high-performance computing architectures. We demonstrate our approach on the liquid-vapor phase transition in superheated water, the unfolding of the chignolin protein, and water dissociation. The latter, performed at the ab initio level, achieves comparable statistical accuracy within days, in contrast to a previous study requiring over a year.

Effect of the Ion, Solvent, and Thermal Interaction Coefficients on Battery Voltage.

In order to increase the adoption of batteries for sustainable transport and energy storage, improved charging and discharging capabilities of lithium-ion batteries are necessary. To achieve this, accurate data that describe the internal state of the cells are essential. Several models have been derived, and transport coefficients have been reported for use in these models. We report for the first time a complete set of transport coefficients to model the concentration and temperature polarization in a lithium-ion battery ternary electrolyte, allowing us to test common assumptions. We include effects due to gradients in chemical potentials and in temperature. We find that the voltage contributions due to salt and solvent polarization are of the same order of magnitude as the ohmic loss and must be taken into account for more accurate modeling and understanding of battery performance. We report new Soret and Seebeck coefficients and find thermal polarization to be significant in cases relevant to battery research. The analysis is suitable for electrochemical systems, in general.

Transport coefficients for ion and solvent coupling. The case of the lithium-ion battery electrolyte.

Transport properties are essential for the understanding and modeling of electrochemical cells, in particular complex systems like lithium-ion batteries. In this study, we demonstrate how a certain degree of freedom in the choice of variables allows us to efficiently determine a complete set of transport properties. We apply the entropy production invariance condition to different sets of electrolyte variables and obtain a general set of formulas. We demonstrate the application of these formulas to an electrolyte typical for lithium-ion batteries, 1M lithium hexafluoro-phosphate in a 1:1 wt. % mixture of ethylene and diethyl carbonates. While simplifications can be introduced, they provide inadequate predictions of conductivity and transport numbers, and we argue that a full matrix of Onsager coefficients is needed for adequate property predictions. Our findings highlight the importance of a complete set of transport coefficients for accurate modeling of complex electrochemical systems and the need for careful consideration of the choice of variables used to determine these properties.

Computational modeling of the molecular basis for the calcium-dependence of the mannuronan C-5 epimerase AvAlgE6 from Azotobacter vinelandii.

The mannuronan C-5 epimerases catalyze epimerization of ß-d-mannuronic acid to α-l-guluronic acid in alginate polymers. The seven extracellular Azotobacter vinelandii epimerases (AvAlgE1-7) are calcium-dependent, and calcium is essential for the structural integrity of their carbohydrate binding R-modules. Ca2+ is also found in the crystal structures of the A-modules, where it is suggested to play a structural role. In this study, the structure of the catalytic A-module of the A. vinelandii mannuronan C-5 epimerase AvAlgE6 is used to investigate the role of this Ca2+. Molecular dynamics (MD) simulations with and without calcium reveal the possible importance of the bound Ca2+ in the hydrophobic packing of ß-sheets. In addition, a putative calcium binding site is found in the active site, indicating a potential direct role of this calcium in the catalysis. According to the literature, two of the residues coordinating calcium in this site are essential for the activity. MD simulations of the interaction with bound substrate indicate that the presence of a calcium ion in this binding site increases the binding strength. Further, explicit calculations of the substrate dissociation pathways with umbrella sampling simulations show and energetically higher dissociation barrier when calcium is present. The present study eludes to a putative catalytic role of calcium in the charge neutralizing first step of the enzymatic reaction. In addition to the importance for understanding these enzymes' molecular mechanisms, this could have implications for engineering strategies of the epimerases in industrial alginate processing.

The influence of temperature on cellulose swelling at constant water density.

We have in this paper investigated how water sorbs to cellulose. We found that both cellulose nanofibril (CNF) and cellulose nanocrystal (CNC) films swell similarly, as they are both mainly composed of cellulose. CNF/CNC films subjected to water at 0.018 kg/m3 at 25 °C and 39 °C, showed a decrease in swelling from ~ 8 to 2%. This deswelling increased the tensile index of CNF-films by ~ 13%. By molecular modeling of fibril swelling, we found that water sorbed to cellulose exhibits a decreased diffusion constant compared to bulk water. We quantified this change and showed that diffusion of sorbed water displays less dependency on swelling temperature compared to bulk water diffusion. To our knowledge, this has not previously been demonstrated by molecular modeling. The difference between bulk water diffusion (DWW) and diffusion of water sorbed to cellulose (DCC) increased from DWW - DCC ~ 3 × 10-5 cm/s2 at 25 °C to DWW - DCC ~ 8.3 × 10-5 cm/s2 at 100 °C. Moreover, water molecules spent less successive time sorbed to a fibril at higher temperatures.

The role of pressure and defects in the wurtzite to rock salt transition in cadmium selenide.

Using molecular dynamics and path sampling techniques we investigated the effect of pressure and defects in the wurtzite to rock salt transition in cadmium selenide (CdSe). In the pressure range 2-10 GPa, rate constants of transition are in the order of 10-23 to 105 s-1 for the transformation of a relatively small wurtzite crystal consisting of 1024 atoms with periodic boundary conditions. The transition paths predominantly evolve through an intermediate 5-coordinated structure, as reported before, though its typical lifetime within the transition paths is particularly long in the intermediate pressure range (4-6 GPa). The defects were created by removing Cd-Se pairs from an otherwise perfect crystal. The removals were either selected fully randomized or grouped in clusters (cavity creation). We find that the rate of transition due to the defects increases by several orders of magnitude even for a single pair removal. This is caused by a change in the transition mechanism that no longer proceeds via the intermediate 5-coordinated structure, when defects are present. Further, the cavity creation yields a lower rate than the fully randomized removal.

Alginate gels crosslinked with chitosan oligomers - a systematic investigation into alginate block structure and chitosan oligomer interaction.

Three alginates with fundamentally different block structures, poly-M, poly-G, and poly-MG, have been investigated upon ionic crosslinking with chitosan oligosaccharides (CHOS), using circular dichroism (CD), rheology, and computer simulations, supporting the previously proposed gelling principle of poly-M forming zipper-like junction zones with chitosan (match in charge distance along the two polyelectrolytes) and revealing a unique high gel strength poly-MG chitosan gelling system. CD spectroscopy revealed an increased chiroptical activity exclusively for the poly-M chitosan gelling system, indicative of induced conformational changes and higher ordered structures. Rheological measurement revealed gel strengths (G' < 900 Pa) for poly-MG (1%) CHOS (0.3%) hydrogels, magnitudes of order greater than displayed by its poly-M analogue. Furthermore, the ionically crosslinked poly-MG chitosan hydrogel increased in gel strength upon the addition of salt (G' < 1600 at 50 mM NaCl), suggesting a stabilization of the junction zones through hydrophobic interactions and/or a phase separation. Molecular dynamics simulations have been used to further investigate these findings, comparing interaction energies, charge distances and chain alignments. These alginates are displaying high gel strengths, are known to be fully biocompatible and have revealed a broad range of tolerance to salt concentrations present in biological systems, proving high relevance for biomedical applications.

Identification of a Pivotal Residue for Determining the Block Structure-Forming Properties of Alginate C-5 Epimerases.

Alginate is a linear copolymer composed of 1→4 linked ß-d-mannuronic acid (M) and its epimer α-l-guluronic acid (G). The polysaccharide is first produced as homopolymeric mannuronan and subsequently, at the polymer level, C-5 epimerases convert M residues to G residues. The bacterium Azotobacter vinelandii encodes a family of seven secreted and calcium ion-dependent mannuronan C-5 epimerases (AlgE1-AlgE7). These epimerases consist of two types of structural modules: the A-modules, which contain the catalytic site, and the R-modules, which influence activity through substrate and calcium binding. In this study, we rationally designed new hybrid mannuronan C-5 epimerases constituting the A-module from AlgE6 and the R-module from AlgE4. This led to a better understanding of the molecular mechanism determining differences in MG- and GG-block-forming properties of the enzymes. A long loop with either tyrosine or phenylalanine extruding from the ß-helix of the enzyme proved essential in defining the final alginate block structure, probably by affecting substrate binding. Normal mode analysis of the A-module from AlgE6 supports the results.

PyRETIS 2: An improbability drive for rare events.

The algorithmic development in the field of path sampling has made tremendous progress in recent years. Although the original transition path sampling method was mostly used as a qualitative tool to sample reaction paths, the more recent family of interface-based path sampling methods has paved the way for more quantitative rate calculation studies. Of the exact methods, the replica exchange transition interface sampling (RETIS) method is the most efficient, but rather difficult to implement. This has been the main motivation to develop the open-source Python-based computer library PyRETIS that was released in 2017. PyRETIS is designed to be easily interfaced with any molecular dynamics (MD) package using either classical or ab initio MD. In this study, we report on the principles and the software enhancements that are now included in PyRETIS 2, as well as the recent developments on the user interface, improvements of the efficiency via the implementation of new shooting moves, easier initialization procedures, analysis methods, and supported interfaced software. © 2019 The Authors. Journal of Computational Chemistry published by Wiley Periodicals, Inc.

Non-equilibrium thermodynamics as a tool to compute temperature at the catalyst surface.

The surface temperature is computed for a heterogeneous catalytic reaction model, namely the oxidation of carbon monoxide on platinum. The surface temperature was found using non-equilibrium thermodynamic theory, a theory which provides the proper dependencies between heat and mass fluxes and the reaction rate. The theory predicts a possible coupling between the reaction rate and the thermal driving force and can help extend classical reaction kinetics. In the absence of direct measurements, we explore the coupling numerically. The results are able to capture experimental data reported in the literature, and give new insights into why Arrhenius plots may turn out to be non-linear.

Local initiation conditions for water autoionization.

The pH of liquid water is determined by the infrequent process in which water molecules split into short-lived hydroxide and hydronium ions. This reaction is difficult to probe experimentally and challenging to simulate. One of the open questions is whether the local water structure around a slightly stretched OH bond is actually initiating the eventual breakage of this bond or whether this event is driven by a global ordering that involves many water molecules far away from the reaction center. Here, we investigated the self-ionization of water at room temperature by rare-event ab initio molecular dynamics and obtained autoionization rates and activation energies in good agreement with experiments. Based on the analysis of thousands of molecular trajectories, we identified a couple of local order parameters and show that if a bond stretch occurs when all these parameters are around their ideal range, the chance for the first dissociation step (double-proton jump) increases from [Formula: see text] to 0.4. Understanding these initiation triggers might ultimately allow the steering of chemical reactions.

Temperature anisotropy at equilibrium reveals nonlocal entropic contributions to interfacial properties.

Density gradient theory for fluids has played a key role in the study of interfacial phenomena for a century. In this work, we revisit its fundamentals by examining the vapor-liquid interface of argon, represented by the cut and shifted Lennard-Jones fluid. The starting point has traditionally been a Helmholtz energy functional using mass densities as arguments. By using rather the internal energy as starting point and including the entropy density as an additional argument, following thereby the phenomenological approach from classical thermodynamics, the extended theory suggests that the configurational part of the temperature has different contributions from the parallel and perpendicular directions at the interface, even at equilibrium. We find a similar anisotropy by examining the configurational temperature in molecular dynamics simulations and obtain a qualitative agreement between theory and simulations. The extended theory shows that the temperature anisotropy originates in nonlocal entropic contributions, which are currently missing from the classical theory. The nonlocal entropic contributions discussed in this work are likely to play a role in the description of both equilibrium and nonequilibrium properties of interfaces. At equilibrium, they influence the temperature- and curvature-dependence of the surface tension. Across the vapor-liquid interface of the Lennard Jones fluid, we find that the maximum in the temperature anisotropy coincides precisely with the maximum in the thermal resistivity relative to the equimolar surface, where the integral of the thermal resistivity gives the Kapitza resistance. This links the temperature anisotropy at equilibrium to the Kapitza resistance of the vapor-liquid interface at nonequilibrium.

PyRETIS: A well-done, medium-sized python library for rare events.

Transition path sampling techniques are becoming common approaches in the study of rare events at the molecular scale. More efficient methods, such as transition interface sampling (TIS) and replica exchange transition interface sampling (RETIS), allow the investigation of rare events, for example, chemical reactions and structural/morphological transitions, in a reasonable computational time. Here, we present PyRETIS, a Python library for performing TIS and RETIS simulations. PyRETIS directs molecular dynamics (MD) simulations in order to sample rare events with unbiased dynamics. PyRETIS is designed to be easily interfaced with any molecular simulation package and in the present release, it has been interfaced with GROMACS and CP2K, for classical and ab initio MD simulations, respectively. © 2017 Wiley Periodicals, Inc.

Rare event simulations reveal subtle key steps in aqueous silicate condensation.

A replica exchange transition interface sampling (RETIS) study combined with Born-Oppenheimer molecular dynamics (BOMD) is used to investigate the dynamics, thermodynamics and the mechanism of the early stages of the silicate condensation process. In this process, two silicate monomers, of which one is an anionic species, form a negatively charged five-coordinated silicate dimer. In a second stage, this dimer can fall apart again, forming the original monomers, or release a water molecule into the solution. We studied the association and dissociation reaction in the gas phase, and the dissociation and water removal step in the aqueous phase. The results on the aqueous phase dissociation suggest two possible mechanisms. The breakage of the bond between the intermediate oxygen and the five-coordinated silicon is sometimes accompanied by a proton transfer. After dissociation into silicate monomers, the anionic monomer is either the previously four-coordinated silicon or the previously five-coordinated silicon depending on whether the hydrogen transfer occurs or not. Our results show that the mechanism of proton transfer is highly predominant. Water removal simulations also show two possible mechanisms distinguished by the proton transfer reaction path. Proton transfer can occur either via a direct or via a water mediated reaction step. The calculations reveal that although both mechanisms contribute to the water removal process, the direct proton transfer is slightly favorable and occurs roughly in six out of ten occasions.

Analyzing Complex Reaction Mechanisms Using Path Sampling.

We introduce an approach to analyze collective variables (CVs) regarding their predictive power for a reaction. The method is based on already available path sampling data produced by, for instance, transition interface sampling or forward flux sampling, which are path sampling methods used for efficient computation of reaction rates. By a search in CV space, a measure of predictiveness can be optimized and, in addition, the number of CVs can be reduced using projection operations which keep this measure invariant. The approach allows testing hypotheses on the reaction mechanism but could, in principle, also be used to construct the phase-space committor surfaces without the need of additional trajectory sampling. The procedure is illustrated for a one-dimensional double-well potential, a theoretical model for an ion-transfer reaction in which the solvent structure can lower the barrier, and an ab initio molecular dynamics study of water auto-ionization. The analysis technique enhances the quantitative interpretation of path sampling data which can provide clues on how chemical reactions can be steered in desired directions.

Coherent description of transport across the water interface: From nanodroplets to climate models.

Transport of mass and energy across the vapor-liquid interface of water is of central importance in a variety of contexts such as climate models, weather forecasts, and power plants. We provide a complete description of the transport properties of the vapor-liquid interface of water with the framework of nonequilibrium thermodynamics. Transport across the planar interface is then described by 3 interface transfer coefficients where 9 more coefficients extend the description to curved interfaces. We obtain all coefficients in the range 260-560 K by taking advantage of water evaporation experiments at low temperatures, nonequilibrium molecular dynamics with the TIP4P/2005 rigid-water-molecule model at high temperatures, and square gradient theory to represent the whole range. Square gradient theory is used to link the region where experiments are possible (low vapor pressures) to the region where nonequilibrium molecular dynamics can be done (high vapor pressures). This enables a description of transport across the planar water interface, interfaces of bubbles, and droplets, as well as interfaces of water structures with complex geometries. The results are likely to improve the description of evaporation and condensation of water at widely different scales; they open a route to improve the understanding of nanodroplets on a small scale and the precision of climate models on a large scale.

Note: A new truncation correction for the configurational temperature extends its applicability to interaction potentials with a discontinuous force.

We present a simple truncation correction for the configurational temperature which, unlike previous corrections, works even at low truncation values for the shifted and truncated Lennard-Jones potential. The success of the new correction suggests that the expression for the configurational temperature is valid also for interaction potentials with a discontinuous force, given that the discontinuity is properly accounted for.

Structural organization of sterol molecules in DPPC bilayers: a coarse-grained molecular dynamics investigation.

We investigate the structural organization of cholesterol (CHOL) analogues in 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) bilayers using coarse-grained molecular dynamics simulations and the MARTINI forcefield. Different sterol molecules are modelled by increasing (CHOLL) or decreasing (CHOLS) the diameter of the sterol beads employed in the MARTINI model of CHOL. At high sterol concentrations, (xsterol = 0.5), typical of liquid ordered phases, we find that the sterol arrangement and sterol-DPPC interactions strongly depend on the sterol size. Smaller sterols (CHOLS and CHOL) form linear clusters, while the larger sterols (CHOLL) arrange themselves into disc shaped clusters. By combining structural and dynamical properties we also investigate the So→ Ld transition for the CHOLL and CHOLS sterols. We show that small changes in the sterol size significantly affect the stability of the gel phase with the gel phase stabilized by the small sterols, but destabilized by large sterols. The general dependence of the phase behaviour of the membrane with sterol content is reminiscent of the one observed in naturally occurring membranes. The relevance of our results to understand current cholesterol-bilayer structural models is discussed.