Complexes of graphene nanoribbons with porphyrins and metal-encapsulated C28 as molecular rectifiers: a theoretical study

The rectification properties of porphyrin–graphene nanoflake complexes and endohedral complexes of C28 fullerene with metal atoms have been studied using the fully ab initio method. D3 dispersion-corrected PBE/-def2-SVP model was used for the optimisations and the electronic energy evaluation. In porphyrin–graphene nanoflake complexes dispersion dominates, while in the endohedral complexes of C28 dispersion does not play an important role. All studied systems do rectify. In the case of fullerenes, the rectification is possible due to the reduction in the molecular symmetry of the fullerene caused by the interaction with electrodes and the endohedral complex formation. The origin of the rectification is the asymmetrical deformation of the electron density under direct and inverse voltages which creates different currents in opposite directions. It seems that peculiar geometry of Au-TPP-Cd/NF diode is responsible for its high rectification ratio. The Cd ion is notably out of the porphyrin plane making close contact with the neighbouring electrode, increasing the asymmetry of the diode compared to other TPP/NF complexes.     

Anti-group A streptococcal vaccine epitope: structure, stability, and its ability to interact with HLA class II molecules

Streptococcus pyogenes infections remain a health problem in several countries due to poststreptococcal sequelae. We developed a vaccine epitope (StreptInCor) composed of 55 amino acids residues of the C-terminal portion of the M protein that encompasses both T and B cell protective epitopes. The nuclear magnetic resonance (NMR) structure of the StreptInCor peptide showed that the structure was composed of two microdomains linked by an 18-residue α-helix. A chemical stability study of the StreptInCor folding/unfolding process using far-UV circular dichroism showed that the structure was chemically stable with respect to pH and the concentration of urea. The T cell epitope is located in the first microdomain and encompasses 11 out of the 18 α-helix residues, whereas the B cell epitope is in the second microdomain and showed no α-helical structure. The prediction of StreptInCor epitope binding to different HLA class II molecules was evaluated based on an analysis of the 55 residues and the theoretical possibilities for the processed peptides to fit into the P1, P4, P6, and P9 pockets in the groove of several HLA class II molecules. We observed 7 potential sites along the amino acid sequence of StreptInCor that were capable of recognizing HLA class II molecules (DRB1*, DRB3*, DRB4*, and DRB5*). StreptInCor-overlapping peptides induced cellular and humoral immune responses of individuals bearing different HLA class II molecules and could be considered as a universal vaccine epitope.     

Effect of the Si,Al and B doping on the sensing behaviour of carbon nanotubes toward ethylene oxide: a computational study

ABSTRACT

Exo– and endo–adsorption of ethylene oxide (EO) on pristine (9,0) (zigzag) carbon nanotube (CNT) and its doped forms with silicon (Si–CNT), aluminum (Al–CNT) and boron (B–CNT) were investigated using density functional theory (DFT) at M06–2X/6–311++G** level. The natural bond orbital (NBO) and the quantum theory of atoms in molecules (QTAIM) analyses were also performed by using the same level of theory. The effect of the doping on sensing behaviour of the CNT toward EO molecule was investigated through intermolecular interactions studies by calculation of total and partial density of states (DOS, PDOS). The enhanced sensitivity of doped–CNTs towards EO molecule associated with adsorption energies (E_ads) and the changes in geometric and electronic structures was examined and the global chemical reactivity parameters were calculated and comprehensively analysed. The thermodynamic property changes were calculated and compared. The results indicated that the EO adsorption on the pristine and doped CNTs was an exothermic spontaneous process. Moreover, based on the calculated E_g change (ΔE_g) and E_ads values, Al–CNT with superior sensitivity for sensing of EO molecule, indicates promising perspectives for its use in fabrication of new EO gas–sensing devices.     

Lewis base interaction with gallium hydrides: a computational study

The recent synthesis and structural characterization of the complex of 3,5-dimethyl-4-hydropyridyl-gallane 1 with the Lewis base 3,5-dimethylpyridine revealed an unusually large angle α = H-Ga-H, 127(2)°, at variance with expected steric effects of the bulky substituents at the tetrahedrally coordinated Ga center. This finding prompted us to study computationally gallium hydrides using density functional and post-Hartree-Fock methods. For 1, we estimated α at 131° from a calculation on 4-hydropyridyl-gallane, GaH₂(Hpy). This value is reduced by 3° due to the interaction with Lewis base pyridine, to yield α = 128°, in excellent agreement with experiment. With an analysis of orbital interactions and a natural bond orbital analysis, we rationalized structural variations of donor-acceptor adducts LGaH₂X where X is a substituent and L is a Lewis base. Angle α is mainly determined by the polarity of the Ga-X bond: the more electronegative substituent X, the larger α and the stronger the interaction of GaH₂X with L. Interaction with a weak base L slightly distorts the initially planar geometry of the dihydride to a trigonal pyramidal form; for a strong base, the structure can become pseudo-tetrahedral.     

Protonation and deprotonation enthalpies of alloxan and implications for the structure and energy of its complexes with water: a computational study

The optimized geometries, harmonic vibrational frequencies, and energies of the structures of monohydrated alloxan were computed at the DFT/ωB97X-D and B3LYP/6–311++G** level of theory. Results confirm that the monohydrate exists as a dipolar alloxan–water complex which represents a global minimum on the potential energy surface (PES). Trajectory dynamics simulations show that attempt to reorient this monohydrate, to a more favorable orientation for H-bonding, is opposed by an energy barrier of 25.07?kJ/mol. Alloxan seems to prefer acting as proton donor than proton acceptor. A marked stabilization due to the formation of N–H–OH₂ bond is observed. The concerted proton donor–acceptor interaction of alloxan with one H₂O molecule does not increase the stability of the alloxan–water complex. The proton affinity of the O and N atoms and the deprotonation enthalpy of the NH bond of alloxan are computed at the same level of theory. Results are compared with recent data on uracil, thymine, and cytosine. The intrinsic acidities and basicities of the four pyrimidines were discussed. Results of the present study reveal that alloxan is capable of forming stronger H-bonds and more stable cyclic complex with water; yet it is of much lower basicity than other pyrimidines.     

Structures and electron affinities of triatomic molecules consisting of Al, P and X (X = B, Al, Ga; C, Si, Ge; N, P, As; O, S and Se)

The structures and electronic properties of the triatomic molecules containing Al, P, X atoms (X = B, Al, Ga; C, Si, Ge; N, P, As; O, S and Se) and their anions are investigated at the B3LYP/cc-PVTZ and the B3LYP/aug-cc-PVTZ levels. The results show that the most stable structures of the anions are AlXP⁻ (X = B, C, N) and PAlX⁻ (X = S, Se), while for the neutral molecules, the most stable structures are PXAl (X = C, N and O). The order of the VDEs of the anions molecules and the AEAs of the neutral species are C < N < O < Si ≈ Ge < P ≈ As < Al = Ga < B < S ≈ Se and C < O < N < Si ≈ Ge < P ≈ As < B < Al ≈ Ga < S ≈ Se, respectively.     

Simplified bacterial "pore" channel provides insight into the assembly, stability, and structure of sodium channels

Eukaryotic sodium channels are important membrane proteins involved in ion permeation, homeostasis, and electrical signaling. They are long, multidomain proteins that do not express well in heterologous systems, and hence, structure/function and biochemical studies on purified sodium channel proteins have been limited. Bacteria produce smaller, homologous tetrameric single domain channels specific for the conductance of sodium ions. They consist of N-terminal voltage sensor and C-terminal pore subdomains. We designed a functional pore-only channel consisting of the final two transmembrane helices, the intervening P-region, and the C-terminal extramembranous region of the sodium channel from the marine bacterium Silicibacter pomeroyi. This sodium "pore" channel forms a tetrameric, folded structure that is capable of supporting sodium flux in phospholipid vesicles. The pore-only channel is more thermally stable than its full-length counterpart, suggesting that the voltage sensor subdomain may destabilize the full-length channel. The pore subdomains can assemble, fold, and function independently from the voltage sensor and exhibit similar ligand-blocking characteristics as the intact channel. The availability of this simple pore-only construct should enable high-level expression for the testing of potential new ligands and enhance our understanding of the structural features that govern sodium selectivity and permeability.     

伤寒Vi多糖菌稳定性研究

为研究国产伤寒Vi多糖菌苗的稳定性,将保存三年以上的伤寒Vi多糖菌苗成品采用自然风干和37℃恒温干燥两种方法浓缩后,用CL－4B柱层析分析系统,测定KD在0．25前多糖的回收率,结果均大于50％,同时对保存三年以上的制品按规程进行了全球,结果均符合规程要求,表明国产菌苗放置三年依然合格。     

Ternary uranyl hydroxo acetate complexes: A computational study of structure, energetics, and stability constants

We studied computationally uranyl monohydroxo monoacetate complexes in aqueous solution using a scalar relativistic all-electron density functional method. Such ternary uranyl complexes may serve as models of ternary uranyl humate complexes which are important for the speciation of uranyl in the environment. As for simple uranyl monocarboxylate complexes, we calculated bidentate coordination to be slightly preferred due to entropy and solvation effects. Compared to uranyl acetate, uranyl hydroxo acetate exhibits an elongated uranyl bond and a short U-OH bond of ∼214 pm. The latter may provide a signature for direct identification of such ternary complexes by EXAFS. As expected from the lower charge of uranyl monohydroxide, complexation by acetate is less exoenergetic than acetate complexation of uranyl. In contrast, experimental complexation constants of uranyl humate and uranyl hydroxo humate are quite similar. Thus, one may question the interpretation of experimental results that assign simple ternary complexes as result of uranyl humate complexation at neutral pH.     

Lotka-Volterra equations: Decomposition,stability, and structure

Summary The major objective of this paper is to propose a new decomposition-aggregation framework for stability analysis of Lotka-Volterra equations employing the concept of vector Liapunov functions. Both the disjoint and the overlapping decompositions are introduced to increase flexibility in constructing Liapunov functions for the overall system. Our second objective is to consider the Lotka-Volterra equations under structural perturbations, and derive conditions under which a positive equilibrium is connectively stable. Both objectives of this paper are directed towards a better understanding of the intricate interplay between stability and complexity in the context of robustness of model ecosystems represented by Lotka-Volterra equations. Only stability of equilibria in models with constant parameters is considered here. Nonequilibrium analysis of models with nonlinear time-varying parameters is the subject of a companion paper.Research supported by U.S. Department of Energy under the Contract EC-77-S-03-1493.On leave from Kobe University, Kobe, Japan.     

The side chain interaction index as a tool for predicting fast-folding elements and the structure and stability of engineered peptides

The side chain interaction index (SCII) is a method of calculating the propensity for short-range interactions among side chains within a peptide sequence. Here, it is shown that the SCII values of secondary structure elements that have been shown to fold early and independently cluster separately from those of structures that fold later and/or are dependent on long-range interactions. In addition, the SCII values of engineered peptides that spontaneously adopt a particular desired fold in solution are significantly different from those of engineered peptides that fail to exhibit a stable conformation. Thus, the SCII, as a measure of local structural stability, constitutes a useful tool in folding prediction and in protein/peptide engineering. A program that allows rapid calculation of SCII values is presented.     

The search for stability on narrow supports: an experimental study in cats and dogs

Kinematic and coordination variables were studied in two carnivorans, one with known locomotor capabilities in arboreal substrates (cat), and the other a completely terrestrial species (dog). Two horizontal substrates were used: a flat trackway on the ground (overground locomotion) and an elevated and narrow runway (narrow-support locomotion). Despite their different degree of familiarity with the ‘arboreal’ situation, both species developed a strategy to adapt to narrow supports. The strategy of cats was based on using slower speeds, coupled with modifications to swing phase duration, to keep balance on narrow supports. The strategy of dogs relied on high speeds to gain in dynamic stability, and they increased cycle frequency by reducing swing phase duration. Furthermore, dogs showed a high variability in limb coordination, although a tendency to canter-like coordination was observed, and also avoided whole-body aerial phases. In different ways, both strategies suggested a reduction of peak vertical forces, and hence a reduction of the vertical oscillations of the centre of mass. Finally, lateral oscillation was reduced by the use of a crouched posture.     

A comparative study on the B12N12, Al12N12, B12P12 and Al12P12 fullerene-like cages

The stability, geometry and electronic structure of the title nanoclusters were compared by using density functional theory (DFT) calculations. Their electrical property analysis showed that the relative magnitude of the HOMO-LUMO gaps (eV) that are average values from the calculated results with five different DFT functionals is as follows: B12N12(7:02)>Al12N12(4.09)>B12P12(3.80)>Al12P12(3.39). Computing the standard enthalpy and the Gibbs free energy of formation, it was found that the B(12)N(12) structure is thermodynamically stable at 298 K and 1 atmosphere of pressure, while the Al(12)N(12) structure may be stable at low temperatures. Due to positive values of change of enthalpy and entropy of formation for both the B(12)P(12) and Al(12)P(12) clusters, it seems that their formation from the consisting atoms is not spontaneous at any temperature.     

Molecular crowding effects on structure and stability of DNA

Living cells contain a variety of biomolecules including nucleic acids, proteins, polysaccharides, and metabolites as well as other soluble and insoluble components. These biomolecules occupy a significant fraction (20-40%) of the cellular volume. The total concentration of biomolecules reaches 400gL(-1), leading to a crowded intracellular environment referred to as molecular crowding. Therefore, an understanding of the effects of molecular crowding conditions on biomolecules is important to broad research fields such as biochemical, medical, and pharmaceutical sciences. In this review, we describe molecular conditions in the cytoplasm and nucleus, which are totally different from in vitro conditions, and then show the biochemical and biophysical consequences of molecular crowding. Finally, we discuss the effect of molecular crowding on the structure, stability, and function of nucleic acids and the significance of molecular crowding in biotechnology and nanotechnology.     

The fluorescent monomeric protein Kusabira Orange. Pressure effect on its structure and stability

The structure and stability of the fluorescent protein monomeric Kusabira Orange (mKO), a GFP-like protein, was studied under different pressure levels and in different chemical environments. At different pH values (between pH 7.4 and pH 4.0) and under a pressure up to 600 MPa (at 25 °C), mKO did not show significant fluorescence spectral changes, indicating a structural stability of the protein. In more extreme chemical conditions (at pH 4.0 in the presence of 0.8 M guanidine hydrochloride), a marked reduction of mKO fluorescence intensity emission was observed at pressures above 300 MPa. This fluorescence emission quenching may be due to the loss of the intermolecular bonds and, consequently, to the destructuration of the mKO chromophore structure. Since the electrostatic and hydrophobic interactions as well as the salt bridges present in proteins are usually perturbed under high pressure, the reduction of mKO fluorescence intensity emission is associated to the perturbation of the protein salt bridges network.     

The cue interaction model of depth perception: a stability analysis

In this paper, we offer a stability analysis of the cue interaction model of depth perception (House (1984)). Depth estimation using stereopsis suffers from the matching problem, the problem of correctly matching the retinal image of a feature in one eye, to its retinal image in the other eye. The Cue Interaction Model overcomes this by using monocular cues to disambiguate between the correct matches and the incorrect matches. Its decision making is based on the concept of cooperation and competition in a neural network. A general class of cooperative and competitive models has been mathematically analysed by Amari and Arbib (1977), with special attention given to equilibrium states and stability. In this paper we adapt their methods to study the above model. In particular, we prove that if the parameters are correctly tuned, the model successfully achieves its goals by suppressing the cues which represent the incorrect matches.Preparation of this paper was supported in part by NIH grant number NS-1 R01 NS24926 from NINCDS     

Mass spectrometry-assisted study reveals that lysine residues 1967 and 1968 have opposite contribution to stability of activated factor VIII

The A2 domain rapidly dissociates from activated factor VIII (FVIIIa) resulting in a dampening of the activity of the activated factor X-generating complex. The amino acid residues that affect A2 domain dissociation are therefore critical for FVIII cofactor function. We have now employed chemical footprinting in conjunction with mass spectrometry to identify lysine residues that contribute to the stability of activated FVIII. We hypothesized that lysine residues, which are buried in FVIII and surface-exposed in dissociated activated FVIII (dis-FVIIIa), may contribute to interdomain interactions. Mass spectrometry analysis revealed that residues Lys(1967) and Lys(1968) of region Thr(1964)-Tyr(1971) are buried in FVIII and exposed to the surface in dis-FVIIIa. This result, combined with the observation that the FVIII variant K1967I is associated with hemophilia A, suggests that these residues contribute to the stability of activated FVIII. Kinetic analysis revealed that the FVIII variants K1967A and K1967I exhibit an almost normal cofactor activity. However, these variants also showed an increased loss in cofactor activity over time compared with that of FVIII WT. Remarkably, the cofactor activity of a K1968A variant was enhanced and sustained for a prolonged time relative to that of FVIII WT. Surface plasmon resonance analysis demonstrated that A2 domain dissociation from activated FVIII was reduced for K1968A and enhanced for K1967A. In conclusion, mass spectrometry analysis combined with site-directed mutagenesis studies revealed that the lysine couple Lys(1967)-Lys(1968) within region Thr(1964)-Tyr(1971) has an opposite contribution to the stability of FVIIIa.     

The structure of NSD1 reveals an autoregulatory mechanism underlying histone H3K36 methylation

The Sotos syndrome gene product, NSD1, is a SET domain histone methyltransferase that primarily dimethylates nucleosomal histone H3 lysine 36 (H3K36). To date, the intrinsic properties of NSD1 that determine its nucleosomal substrate selectivity and dimethyl H3K36 product specificity remain unknown. The 1.7 Å structure of the catalytic domain of NSD1 presented here shows that a regulatory loop adopts a conformation that prevents free access of H3K36 to the bound S-adenosyl-l-methionine. Molecular dynamics simulation and computational docking revealed that this normally inhibitory loop can adopt an active conformation, allowing H3K36 access to the active site, and that the nucleosome may stabilize the active conformation of the regulatory loop. Hence, our study reveals an autoregulatory mechanism of NSD1 and provides insight into the molecular mechanism of the nucleosomal substrate selectivity of this disease-related H3K36 methyltransferase.     

Inhibition of cathepsin B by Au(I) complexes: a kinetic and computational study

Gold(I) compounds have been used in the treatment of rheumatoid arthritis for over 80 years, but the biological targets and the structure–activity relationships of these drugs are not well understood. Of particular interest is the molecular mechanism behind the antiarthritic activity of the orally available drug triethylphosphine(2,3,4,6-tetra-O-acetyl-β-1-d-thiopyranosato-S) gold(I) (auranofin, Ridaura). The cathepsin family of lysosomal, cysteine-dependent enzymes is an attractive biological target of Au(I) and is inhibited by auranofin and auranofin analogs with reasonable potency. Here we employ a combination of experimental and computational investigations into the effect of changes in the phosphine ligand of auranofin on its in vitro inhibition of cathepsin B. Sequential replacement of the ethyl substituents of triethylphosphine by phenyl groups leads to increasing potency in the resultant Au(I) complexes, due in large part to favorable interactions of the more sterically bulky Au(I)–PR₃ fragments with the enzyme active site.