Earticle

Computer-aided drug design uses computational chemistry to discover, enhance, or study drugs and related biologically active molecules. It is now proved to be effective in reducing costs and speeding up drug discovery. In this short review, we discussed on the importance of combining molecular docking and molecular dynamics simulation methodologies. We also reviewed the importance of protein flexibility, refinement of docked complexes using molecular dynamics and the use of free energy calculations for the calculation of accurate binding energies has been reviewed.

Amyloid oligomers are believed to play important causal roles in many types of amyloid-related degenerative diseases. Many different laboratories have reported amyloid oligomers that differ in size, morphology, toxicity, and method of preparation or purification, raising the question of the structural relationships among these oligomer preparations. The structural plasticity that has been reported to occur in amyloid formed from the same protein sequence indicates that it is quite possible that different oligomer preparations may represent distinct structural variants. In view of the difficulty in determining the precise structure of amyloids, conformation- and epitope-specific antibodies may provide a facile means of classifying amyloid oligomer structures. Conformation-dependent antibodies that recognize generic epitopes that are specifically associated with distinct aggregation states of many different amyloid-forming sequences indicate that there are at least two fundamentally distinct types of amyloid oligomers: fibrillar and prefibrillar oligomers. Classification of amyloid oligomers according to their underlying structures may be a more useful and rational approach than relying on differences in size and morphology.

Amyloid beta (Aβ) peptide has been implicated in the pathogenesis of Alzheimer’s disease and has been reported to induce apoptotic death in cell culture. Cysteine Proteases, a family of enzymes known as caspases, mediate cell death in many models of apoptosis. In the present study, we examined the caspase activity and cell death in Aβ -treated SHSY5Y cells, as an attempt to elucidate the relationship between the type of caspase and Aβ-induced cell death. Aβ at 20 μM induce activation of caspase-3, 8 and 9 activity, but not the caspase-1. Caspase-3, 8 and 9 were processed by Ab treatment, consistent with the activity assay. Inhibition of the caspase activities by the selective inhibitors, however, marginally affected the cell death induced by Aβ. Taken together, the results indicate that Aβ-induced cell death may be independent of caspase activity and rather, the enzymes might be activated as a result of the cell death.

The crystal structure of the title compounds with both coumarin and sulfonamide moieties were examined. These two groups have very special for their pharmaceutical and medicinal properties have been determined from single crystal Xray diffraction data. In the title compound crystallizes in the monoclinic space group C2/c with unit cell dimension a = 28.633(3) Å, b= 9.3215(7) Å and c= 24.590(2) Å [alpha & gamma=90o beta= 115.976(3)o]. In the structure The S1 atom shows a distorted tetrahedral geometry, with O1—S1—O2 [119.74 (2)°] and N1-S1-C5 [105.57(1)o] angles deviating from ideal tetrahedral values are attributed to the Thrope-Ingold effect. The sum of bond angles around N1 (316.2(1)o) indicates that N1 is in sp2 hybridization. The Pyridine ring adopts boat conformation and pyran rings adopt a sofa conformation. The carboxylate group of atoms were disordered over two positions with site occupancy factors 0.598 (9):0.402 (9). Crystal structure and packing is stabilized by C-H…O intra and inter molecular hydrogen bond interactions.

Caspase-12, mainly detected in endoplasmic reticulum (ER), has been suggested to play a role in ER- mediated apoptosis and inflammatory caspase activation pathway. Removal of the prodomain by caspase-3/-7 at Asp94 or m -calpain at Lys158 was reported to be a part of caspase-12-involved (in) apoptosis. To provide biochemical background for the processes, we purified and characterized three forms of caspase-12; Δpro1(G95-D419), rev-Δpro1[(T319-N419)- (G95-D318), a reverse form of Δpro1] and rev-Δpro2[(T319-N419)-(T159-D318)]. Activity of Δpro1, comparable (in compare) to those of the other two, decreased significantly under the physiological salt concentration and pH or by mutations at both Asp318 and Asp320. These indicated (indicate) that activation of caspase-12 may need pH drop and ion efflux observed during apoptotic process, and auto-proteolytic cleavage at the sites. Furthermore, constitutively active forms of caspase-12 could induce cell death, but no cleavage of caspase-3, DFF45 and Bid was observed, implying involvement of caspase-12 in a distinct way rather than in the well-known pathway.

Synthesis of long or aggregation-prone peptide has been problematic chemically. Its biological production has an advantage in that point, but it often forms inclusion body which creates difficulties in recovery of targets. As a deubiquitylating enzyme (Usp2-cc) was shown in this study to maintain its activity even in the presence of up to 4 M urea, target peptide was purified by a single step of chromatography after overexpression as inclusion body, solubilization in urea and cleavage by the enzyme from the fusion protein consisting of GroES (used for high expression and easy to handle), ubiquitin (as a cleavage site) and target peptide. This system is a convenient tool for production of peptides that are difficult to be chemically synthesized and biologically purified.

When a hydrophobic and hydrophilic environments of bis(2,2'-bipyridyl) copper(II) (Cu(bpy)2 2+) are produced in the presence of anionic surfactant sodium dodecyl sulfate (SDS), cyclic voltammetry is used to investigate the microscopic environments which occurs at the glassy carbon electrode. In order to see the relation between ΔE p and a critical micelle concentration (CMC), ΔE p vs. -Log[SDS] for the redox couples are plotted. The concentration at the intersection of two lines is 2.57 mM SDS, and this concentration can be determined as the CMC (relative error: below 0.03%; 2.63 mM SDS by surface tensiometry).

In this paper, we construct an logarithmic spiral-like curve using curvature-continuous quadratic spline and quadratic rational spline. The quadratic (rational) spline has self-similarity. We present some properties of the quadratic spline. Also using this G2 quadratic spline, an approximation of logarithmic spiral is proposed and error analysis is obtained.

Resins were synthesized by mixing N-phenylaza-15-crown-5 macrocyclic ligand attached to styrene (2th petroleum in 4th class hazardous materials) divinylbenzene (DVB) copolymer with crosslink of 1%, 2%, 6%, and 12% by substitution reaction. The synthesis of these resins was confirmed by content of chlorine, element analysis, thermo gravimetric analysis (TGA), surface area, and IR-spectroscopy. The effects of pH, equilibrium arrival time, dielectric constant of solvent and crosslink on adsorption of metal ions　by the synthetic resin adsorbent were investigated. The metal ions were showed fast adsorption on the resins above pH 4. The optimum equilibrium time for adsorption of metallic ions was about two hours. The adsorption selectivity determined in ethanol was in increasing order uranium (VI) > zinc (II) > europium (III) ions. The uranium ion adsorbed in the order of 1%, 2%, 6%, and 12% crosslink resin and adsorption of resin decreased in proportion to the order of dielectric constant of solvents.

Fisher information matrix plays an important role in statistical inference of unknown parameters. Especially, it is used in objective Bayesian inference where we calculate the posterior distribution using a noninformative prior distribution, and also in an example of metric functions in geometry. To estimate parameters in a distribution, we can use the Fisher information matrix. The more the number of parameters increases, the more its matrix form gets complicated. In this paper, by using Mathematica programs we derive the Fisher information matrix for 4-parameter generalized gamma distribution which is used in reliability theory.

Let Tn(x) be the Chebyshev polynomials of first kind of degree n. In this paper, we show that for a >1, the polynomial with integer coefficients Tn(z)-Tn(a)/z-a has all its roots in IzI≤a.