A computational study of the effect of an external electric field on the geometry of selected donor–acceptor complexes

To understand the effect of Au and thiol atoms in octane molecule, a structural and charge density analysis has been carried out by high level ab initio quantum chemical calculations using MP2 and B3PW91 methods with the basis sets 6-311G(d,p) and LANL2DZ. The optimized geometries, specifically, the geometry obtained from both levels reveal the effect of S- and Au-atoms in octane molecule. An introduction of sulfur atom in octane molecule lengthen its backbone C–C bond distances, and further adding of Au-atom at the terminals of octane dithiolate stabilizes these distances. The bond densities of the C–C bonds of octane are 1.6 eÅ⁻³, these values are decreased significantly and the charges are largely depleted, when thiol and Au-atoms added in the octane molecule. The presence of negative Laplacian ²ρ(r) at bond critical points of C–C and C–H bonds, indicate, the charges are concentrated in these bonds, confirm that these bonds exhibit an open shell type interaction. The moderate values of density and the negative Laplacian of S–C bonds confirm the covalent character. The positive ²ρ(r) value of Au–S bonds, characterize, the bonding interaction is a closed shell interaction. The combined observed low value of electron density and the positive Laplacian of Au–S bond comprises, the gold and S interaction is not a covalent interaction, but it is a very weak coordination bond interaction. The small positive value of total energy density in Au–S bond indicates, the charges in these bonds are highly depleted and this is further confirmed by the Laplacian of bond characterization.     

Orbits of parabolic subgroups on metabelian ideals

Let k be an algebraically closed field, t∈Z?1, and let B be the Borel subgroup of GLt(k) consisting of upper-triangular matrices. Let Q be a parabolic subgroup of GLt(k) that contains B and such that the Lie algebra qu of the unipotent radical of Q is metabelian, i.e. the derived subalgebra of qu is abelian. For a dimension vector with , we obtain a parabolic subgroup P(d) of GLn(k) from B by taking upper-triangular block matrices with (i,j) block of size di×dj. In a similar manner we obtain a parabolic subgroup Q(d) of GLn(k) from Q. We determine all instances when P(d) acts on qu(d) with a finite number of orbits for all dimension vectors d. Our methods use a translation of the problem into the representation theory of certain quasi-hereditary algebras. In the finite cases, we use Auslander-Reiten theory to explicitly determine the P(d)-orbits; this also allows us to determine the degenerations of P(d)-orbits.     

NMR distinction of single- and multiple-mode binding of small-molecule protein ligands

Identifying and characterizing small-molecule inhibitors of protein-protein interactions is of high interest for drug discovery and for chemical genetics studies of biological pathways. Very often, initial hits or first-generation compounds have low micromolar dissociation constants and cause line broadening in NMR spectra. It is very important for subsequent structure-based compound optimization to know if this line broadening is caused by intermediate exchange of the dissociation kinetics only or in addition by multiple binding modes. Here, we present an approach of how to distinguish these two situations and demonstrate its experimental application. Two very similar small-molecule ligands of Bcl-xL are considered that cause both severe line broadening of interface residues. We show that one compound exhibits single-mode binding, and broadening is just due to dissociation kinetics in the intermediate exchange regime, and the line broadening can be overcome by providing excess ligand. In the other case, line broadening is due to dissociation kinetics and exchange between multiple bound conformations, and broadening cannot be overcome by providing excess ligand. The procedures used are very general and can also be applied to characterizing protein-protein and protein-nucleic acid interactions.     

A general polymer-based process to prepare mixed metal oxides: the case of Zn1-xMgxO nanoparticles

Nanometer-sized mixed metal oxide (MMO) particles (Zn1-xMgxO) with very precise stoichiometry are prepared employing a polymer-based method. The precursor is formed by loading a polyacrylate with metal ions followed by purification of the polymer metal ion complex via repeated precipitation/redissolution cycles. Calcination of the polymer precursor at 550 degrees C gives particles of the metastable solid solution of the ZnO/MgO system in the composition range (x<0.2 and x>or=0.82). The MMO crystal particles are typically 20-50 nm in diameter. Doping of the ZnO by Mg2+ causes a shrinkage of lattice parameter c. Effects of band gap engineering on the optical band gap are reported. The photoluminescence in the visible is also affected, and its maximum shifts from 2.12 eV (pure ZnO) to 2.32 eV at x=0.21. The crystalline MMO particles start to undergo segregation into hexagonal and cubic phases upon annealing at 800 degrees C.     

Effects of electric fields on proton transport through water chains

Molecular dynamics simulations on quantum energy surfaces are carried out to study the effects of perturbing electric fields on proton transport (PT) in protonated water chains. As an idealized model of a hydrophobic cavity in the interior of a protein the water molecules are confined into a carbon nanotube (CNT). The water chain connects a hydrated hydronium ion (H3O+) at one end of the CNT and an imidazole molecule at the other end. Without perturbing electric fields PT from the hydronium proton donor to the imidazole acceptor occurs on a picosecond time scale. External perturbations to PT are created by electric fields of varying intensities, normal to the CNT axis, generated by a neutral pair of charges on the nanotube wall. For fields above approximately 0.5 VA, the hydronium ion is effectively trapped at the CNT center, and PT blocked. Fields of comparable strength are generated inside proteins by nearby polar/charged amino acids. At lower fields the system displays a rich dynamic behavior, where the excess charge shuttles back and forth along the water chain before reaching the acceptor group on the picosecond time scale. The effects of the perturbing field on the proton movement are analyzed in terms of structural and dynamic properties of the water chain. The implications of these observations on PT in biomolecular systems and its control by external perturbing fields are discussed.     

Comparison of different separation technologies for proteome analyses: isoform resolution as a prerequisite for the definition of protein biomarkers on the level of posttranslational modifications

In this article we evaluate methods used to reveal the molecular complexity, which is generated in biological samples by posttranslational modifications (PTM) of proteins. We show how distinct molecular differences on the level of phosphorylation sites in a single protein (ovalbumin) can be resolved with different success using 1D and 2D gel-electrophoresis and reversed-phase liquid chromatography (LC) with monolithic polystyrol-divinylbenzol (PS-DVB) columns for protein separation, and matrix-assisted laser desorption ionisation-time of flight mass spectrometry (MALDI-TOF MS) for protein identification. Phosphorylation site analysis was performed using enzymatic dephosphorylation in combination with differential peptide mass mapping. Liquid chromatography-MALDI-TOF MS coupling with subsequent on-target tryptic protein digestion turned out to be the fastest method tested but yielded low resolution for the analysis of PTM, whereas 2D gel-electrophoresis, due to its unique capability of resolving highly complex isoform pattern, turned out to be the most suitable method for this purpose. The evaluated methods complement one another and in connection with efficient technologies for differential and quantitative analysis, these approaches have the potential to reveal novel molecular details of protein biomarkers.     

Phase behavior of a symmetrical binary fluid mixture

We have investigated the phase behavior of a symmetrical binary fluid mixture for the situation where the chemical potentials mu(1) and mu(2) of the two species differ. Attention is focused on the set of interparticle interaction strengths for which, when mu(1)=mu(2), the phase diagram exhibits both a liquid-vapor critical point and a tricritical point. The corresponding phase behavior for the case mu(1) not equalmu(2) is investigated via integral-equation theory calculations within the mean spherical approximation and grand canonical Monte Carlo (GCMC) simulations. We find that two possible subtypes of phase behavior can occur, these being distinguished by the relationship between the triple lines in the full phase diagram in the space of temperature, density, and concentration. We present the detailed form of the phase diagram for both subtypes and compare with the results from GCMC simulations, finding good overall agreement. The scenario via which one subtype evolves into the other is also studied, revealing interesting features.     

Multiple time step update schemes for dissipative particle dynamics

In dynamical simulations of coarse-grained models of soft matter in a solvent a considerable amount of the total simulation time is generically spent on updating the solvent particles, although their dynamics is in most cases not of primary interest. In order to speed up such simulations and as a consequence allow to extend them to cover larger system sizes, we propose and examine various multiple, specifically dual, time step update algorithms for dissipative particle dynamics simulations that are based on the velocity-Verlet scheme [Phys. Rev. 159, 98 (1967)]. Common to all update variants is that the solvent beads are updated with a lower frequency than the bonded interactions within the solute. As a test case we consider a coarse-grained model of a lipid bilayer in water. Our results demonstrate that a considerable saving of simulation time can be gained, while the obtained simulation data are within error brackets virtually identical to those obtained for the reference single time step update scheme.