Determination of alkali and halide monovalent ion parameters for use in explicitly solvated biomolecular simulations

Alkali (Li(+), Na(+), K(+), Rb(+), and Cs(+)) and halide (F(-), Cl(-), Br(-), and I(-)) ions play an important role in many biological phenomena, roles that range from stabilization of biomolecular structure, to influence on biomolecular dynamics, to key physiological influence on homeostasis and signaling. To properly model ionic interaction and stability in atomistic simulations of biomolecular structure, dynamics, folding, catalysis, and function, an accurate model or representation of the monovalent ions is critically necessary. A good model needs to simultaneously reproduce many properties of ions, including their structure, dynamics, solvation, and moreover both the interactions of these ions with each other in the crystal and in solution and the interactions of ions with other molecules. At present, the best force fields for biomolecules employ a simple additive, nonpolarizable, and pairwise potential for atomic interaction. In this work, we describe our efforts to build better models of the monovalent ions within the pairwise Coulombic and 6-12 Lennard-Jones framework, where the models are tuned to balance crystal and solution properties in Ewald simulations with specific choices of well-known water models. Although it has been clearly demonstrated that truly accurate treatments of ions will require inclusion of nonadditivity and polarizability (particularly with the anions) and ultimately even a quantum mechanical treatment, our goal was to simply push the limits of the additive treatments to see if a balanced model could be created. The applied methodology is general and can be extended to other ions and to polarizable force-field models. Our starting point centered on observations from long simulations of biomolecules in salt solution with the AMBER force fields where salt crystals formed well below their solubility limit. The likely cause of the artifact in the AMBER parameters relates to the naive mixing of the Smith and Dang chloride parameters with AMBER-adapted Aqvist cation parameters. To provide a more appropriate balance, we reoptimized the parameters of the Lennard-Jones potential for the ions and specific choices of water models. To validate and optimize the parameters, we calculated hydration free energies of the solvated ions and also lattice energies (LE) and lattice constants (LC) of alkali halide salt crystals. This is the first effort that systematically scans across the Lennard-Jones space (well depth and radius) while balancing ion properties like LE and LC across all pair combinations of the alkali ions and halide ions. The optimization across the entire monovalent series avoids systematic deviations. The ion parameters developed, optimized, and characterized were targeted for use with some of the most commonly used rigid and nonpolarizable water models, specifically TIP3P, TIP4P EW, and SPC/E. In addition to well reproducing the solution and crystal properties, the new ion parameters well reproduce binding energies of the ions to water and the radii of the first hydration shells.     

Metal‐Free Hydrosilylation Polymerization by Borane Catalyst

The first example of metal‐free hydrosilylation polymerization between dienes and disilanes is developed by using a borane catalyst, B(C₆F₅)₃ to replace precious transition‐metal‐based systems. Under the easy‐to‐handle and mild conditions, a step‐growth polymerization of two readily available diene and disilane units was achieved with high degrees of polymerization. Various combinations of dienes and disilanes produced polycarbosilanes with a broad range of structures and properties.     

Application of a continued-fraction-based theory to magneto-optical intraband transition in GaAs and CdS

The quantum theory of intraband magneto-optical transition in semiconductors introduced previously in terms of continued-fraction-based power-series-expansion technique is reviewed in connection with examination of temperature- and dimensional-dependence of the width in GaAs and CdS in which piezoelectric scattering is dominant. With the same values of the piezoelectric coupling constant K and the expansion parameter the width in two-dimensions increases with temperature as in three-dimensions. Furthermore, the width becomes smaller uniformly as the dimension is reduced in the direction of static magnetic field in the quantum limit, which is physical. Therefore, the continued-fraction-based theory gives quite good interpretation of the acoustic phonon scattering in the quantum limit.     

Cubic interactions of massless higher spins in (A)dS: Metric-like approach

Cubic interactions of higher-spin gauge fields in (A)d_Sd$(A)d{S}_d$ are studied in the metric-like approach. Making use of the traceless and transverse constraints together with the ambient-space formalism, all consistent parity-invariant cubic vertices are obtained for d?4$d?4$ in a closed form pointing out the key role of their flat-space counterparts.     

Potential of Ramalin and Its Derivatives for the Treatment of Alzheimer’s Disease

The pathogenesis of Alzheimer’s disease (AD) is still unclear, and presently there is no cure for the disease that can be used for its treatment or to stop its progression. Here, we investigated the therapeutic potential of ramalin (isolated from the Antarctic lichen, Ramalina terebrata), which exhibits various physiological activities, in AD. Specifically, derivatives were synthesized based on the structure of ramalin, which has a strong antioxidant effect, BACE-1 inhibition activity, and anti-inflammatory effects. Therefore, ramalin and its derivatives exhibit activity against multiple targets associated with AD and can serve as potential therapeutic agents for the disease.     

Immobilization of growing cells by polyethyleneimine-modified alginate

A unique polymer matrix that is suitable for immobilizing growing cells has been developed. Alginate was chemically modified with polyethyleneimine (PEI), and the resultant polymer aggregate was evaluated as a cell carrier. Our method of immobilization depends on reversible gelation of the PEI-modified alginate. Our hypothesis is that immobilized cells grow by dissolving the surrounding gel matrix; the dissolved polymer adduct is displaced peripherally and gelled again by the influx of calcium ion from the surrounding fermentation broth, retaining both cells and carrier polymer in the gel beads. Thus, the immobilized cells gain space for growth by expanding the carrier matrix. The PEI modification offers the following advantages: (1) improved mechanical strength; (2) improved cell retention; (3) increased catalyst life; (4) ease of pelletization; and (5) an apparent bacteriostatic capability. When immobilized yeast cells were applied to a continuous ethanol fermentation, 94% theoretical conversion of glucose to ethanol was observed, with a reactor productivity of 15–30 g/L/h in a nonsterile reactor. A 3-mo catalyst life and minimal cell washout were observed.     

Relationship between flavonoid structure and inhibition of farnesyl protein transferase

Flavonoids are well-known phytochemicals that are produced by various plants in high quantities. The chemopreventive activity of flavonoids is dependent on their structural features. The studies of structure-FPTase inhibitory activity indicated that the number, position and substitution of hydroxyl groups of the A and B rings of flavonoid, and unsaturation of the C2-C3 bond are important factors affecting inhibition on FPTase by flavonoids. A couple of flavonoids inhibited FPTase and also the growth of human tumor cell lines, especially butein, which strongly inhibited the growth of colon cancer cell line (HCT116). However, flavanones and flavanols did not inhibit FPTase nor the growth of tumor cells.     

Sonication treatment of CdTe/CdS semiconductor nanocrystals and their bio-application

Ultrasonic irradiation of core/shell structures was shown to lead to low toxicity and high quantum yields relative to thermal methods for bio-application.