Discrete water domains in hydrophobic environment find relevance in aerosols, oil refinery, the human body, etc. The interfacial microstructure plays a crucial role in the stability of such water domains. Over the decades, the amphiphile-induced electrostatic interaction is considered to be the major stabilizing factor operating at these interfaces. Here we take the representative water/AOT/oil microemulsion to show that creating a strong Hbonding network through suitable additive, such as protic ionic liquid (IL) at the interface, helps both the growth and stability of water domains in the hydrophobic phase. On the other hand, common electrolytes and aprotic ILs fail to replicate such behavior as seen by Raman, Fourier transform infrared spectroscopy, dynamic light scattering (DLS), and electron microscopy measurements. Experimental results are further supported by the all-atomic molecular dynamics (MD) simulations that showed extended Hbonding mediated by the protic IL cations that were localized at the interface. High temperature DLS and rheology studies have shown greater thermal stability and mechanical strengths of our biocompatible microemulsions, which have potential to become suitable templates for in situ synthesis of nanoparticle and various organic compounds.

Ionic liquids (ILs) are designer solvents that find wide applications in various areas. Recently, ILs have been shown to induce the refolding of certain proteins that were previously denatured under the treatment of urea. A molecular-level understanding of the counteracting mechanism of ILs on urea-induced protein denaturation remains elusive. In this study, we employ atomistic molecular dynamics simulations to investigate the ternary urea–water–IL solution in comparison to the aqueous urea solution to understand how the presence of ILs can modulate the structure, energetics, and dynamics of urea–water solutions. Our results show that the ions of the IL used, ethylammonium nitrate (EAN), interact strongly with urea and disrupt the urea aggregates that were known to stabilize the unfolded state of the proteins. Results also suggest a disruption in urea–water interaction that releases more free water molecules in solution. We subsequently strengthened these findings by simulating a model peptide in the absence and presence of EAN, which showed broken versus intact secondary structure in urea solution. Analyses show that these changes were accomplished by the added IL, which enforced a gradual displacement of urea from the peptide surface by water. We propose that the ILs facilitate protein renaturation by breaking down the urea aggregates and increasing the amount of free water molecules around the protein.

Ionic liquid−water binary solutions have significantly expanded the applications of ionic liquids (ILs) in chemical and biological research. Therefore, considerable research has focused on measuring the thermophysical properties of these binary mixtures. From low-to-moderate concentrations of water, several IL/water mixtures exhibit deviations from expected trends in thermophysical behavior. One such example is a unique density trend observed for certain IL classes, which exhibit a characteristic increase in density with the addition of small amounts of water. Since water primarily interacts with the IL anion, such deviations have always been explained in the context of anion−water associations. Surprisingly, however, IL/water mixtures containing different cations but a common lactate anion exhibit similar peculiarities in density trends. Using atomistic level molecular dynamics simulations, we show that diverse density trends are caused by cation-mediated modulations in the IL nanostructure. Depending on its nature, the IL cation can play a dual role in modulating the IL nanostructure: (i) resist water-mediated breakdown of the nanostructure by interacting with the anion very strongly, (ii) further strengthen the nanostructure by incorporating water in the IL framework. The [emim] cation fails to play both roles resulting in the density decrease, while the [tmg] cation fulfills both roles leading to a density rise. The choline cation resists the density fall by inducing the formation of "water-clathrates" in the solution. Such occurrence of clathrates in IL/water binary mixtures, reported for the first time in this study, further emphasizes that the properties of ILs and its mixtures are not merely determined by the chemical nature of the component ions, but also by their unique nanostructural organizations. These unique nanostructural organizations also manifest in their unusual dynamics.

Rapid spread of ZIKA virus (ZIKV) and its association with severe birth defects have raised worldwide concern. Recent studies have shown that ZIKV retains its infectivity and remains structurally stable at temperatures up to 40 °C, unlike dengue and other flaviviruses. In spite of recent cryo-EM structures that showed similar architecture of ZIKA and dengue virus (DENV) E protein shells, little is known that makes ZIKV so temperature insensitive. Here, we attempt to unravel the molecular basis of greater thermal stability of ZIKV over DENV2 by executing atomistic molecular dynamics (MD) simulations on the viral E protein shells at 37 °C. Our results suggest that ZIKA E protein shell retains its structural integrity through stronger inter-raft communications facilitated by a series of electrostatic and H-bonding interactions among multiple inter-raft residues. In comparison, the DENV2 E protein shell surface was loosly packed that exhibited holes at all 3-fold vertices, in close agreement with another EM structure solved at 37 °C. The residue-level information obtained from our study could pave way for designing small molecule inhibitors and specific antibodies to inhibit ZIKV E protein assembly and membrane fusion.

No abstract

The local conformation of DNA plays a critical role in the recognition-andbinding process of transcription factors. In particular, the most common form of the DNA double helix, B-DNA, exists as a conformational equilibrium between BI and BII substates that are associated with changes in major and minor groove dimensions. It has been hypothesized that cytosine methylation, the most common epigenetic modification and one that is often found in so-called CpG islands, modulates transcription factor binding affinity by altering the BI-BII equilibrium in the neighborhood of methylation sites. Indeed, previous molecular dynamics studies have suggested that cytosine methylation leads to a uniform stabilization of the BI substate in CpG islands. In this work we first benchmark the ability of the latest Amber DNA force fields and a variety of three-point water models to reproduce BI-BII equilibrium in the Dickerson dodecamer and reduce terminal base pair fraying. Using the best-performing combinations, we then re-examine the conformational effects of cytosine methylation in a prototypical CpG island, (GC) 5 . We find that the BI substate is stabilized for GpC steps in such sequences, but that the BII substate is stabilized for the CpG steps. More interestingly, the Amber ff99bsc0 DNA force field used in previous studies yields opposite conclusions. These findings highlight the need for continued fixed-charge force field development for nucleic acids, as well as solution state experimental datasets involving epigenetic modification that can serve as benchmarks for simulation accuracy.