Identification of Druggable Targets for Acinetobacter baumannii Via Subtractive Genomics and Plausible Inhibitors for MurA and MurB

Emergence of the multidrug-resistant pathogens has rendered the current therapies ineffective thereby, resulting in the need for new drugs and drug targets. The accumulating protein sequence data has initiated a drift from classical drug discovery protocols to structure-based drug designing. In the present study, in silico subtractive genomics approach was implemented to find a set of potential drug targets present in an opportunist bacterial pathogen, Acinetobacter baumannii (A. baumannii). Out of the 43 targets identified, further studies for protein model building and lead-inhibitor identification were carried out on two cell-essential targets, MurA and MurB enzymes (of A. baumannii designated as MurA_Ab and MurB_Ab) involved in the peptidoglycan biosynthesis pathway of bacteria. The homology model built for each of them was further refined and validated using various available programs like PROCHECK, Errat, ProSA energy plots, etc. Compounds showing activity against MurA and MurB enzymes of other organisms were collected from the literature and were docked into the active site of MurA_Ab and MurB_Ab enzymes. Three inhibitors namely, T6361, carbidopa, and aesculin, showed maximum Glide score, hydrogen bonding interactions with the key amino acid residues of both the enzymes and acceptable ADME properties. Furthermore, molecular dynamics simulation studies on MurA_Ab–T6361 and MurB_Ab–T6361 complexes suggested that the ligand has a high binding affinity with both the enzymes and the hydrogen bonding with the key residues were stable in the dynamic condition also. Therefore, these ligands have been propsed as dual inhibitors and promising lead compounds for the drug design against MurA_Ab and MurB_Ab enzymes.     

Approximate controllability of retarded semilinear stochastic system with non local conditions

This paper deals with the approximate controllability of retarded semilinear stochastic system with nonlocal conditions in Hilbert Spaces under the assumption that the corresponding linear system is approximately controllable. The control function for this system is suitably constructed by using the infinite dimensional controllability operator. With this control function, the sufficient conditions for the approximate controllability of the proposed problem in Hilbert Space are established. The results are obtained by using Banach fixed point theorem. Finally, two examples are provided to illustrate the application of the obtained results.     

An O(k2 + kh2 + h4) arithmetic average discretization for the solution of 1‐D nonlinear parabolic equations

This article develops a new two‐level three‐point implicit finite difference scheme of order 2 in time and 4 in space based on arithmetic average discretization for the solution of nonlinear parabolic equation ε u_xx = f(x, t, u, u_x, u_t), 0 < x < 1, t > 0 subject to appropriate initial and Dirichlet boundary conditions, where ε > 0 is a small positive constant. We also propose a new explicit difference scheme of order 2 in time and 4 in space for the estimates of (?u/?x). The main objective is the proposed formulas are directly applicable to both singular and nonsingular problems. We do not require any fictitious points outside the solution region and any special technique to handle the singular problems. Stability analysis of a model problem is discussed. Numerical results are provided to validate the usefulness of the proposed formulas. © 2006 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq, 2007     

X-ray Topographic Assessment of Defects in Pure and Substituted Hexaferrite Crystals

Results of X-ray diffraction topography, in reflection and transmission scanning geometry, of flux grown single crystals of substituted and unsubstituted hexaferrites bearing composition SrGa_xIn_yFe_12-(x+y)O₁₉ (where x = 0, 5, 7, 9; y = 0, 0.8, 1.3, 1.0) are presented. Diffraction topographs reveal defects like misoriented grains, dislocations, cavities, inclusions, and the strain patterns in these crystals. The unsubstituted hexaferrites exhibit better perfection when compared to the substituted ones. The study is reported to support the results obtained by chemical etching and fractography, besides yielding additional information covering defects.     

BOOK REVIEW

Land Resource Economics and Sustainable Development: Economic Policies and the Common Good, G. Cornelis van Kooten, UBC Press, Vancouver, 1993, 450 pp.     

On Rivlin-Erickson elastico-viscous fluid heated and soluted from below in the presence of compressibility, rotation and hall currents

A layer of compressible, rotating, elastico-viscous fluid heated & soluted from below is considered in the presence of vertical magnetic field to include the effect of Hall currents. Dispersion relation governing the effect of viscoelasticity, salinity gradient, rotation, magnetic field and Hall currents is derived. For the case of stationary convection, the Rivlin-Erickson fluid behaves like an ordinary Newtonian fluid. The compressibility, stable solute gradient, rotation and magnetic field postpone the onset of thermosolutal instability whereas Hall currents are found to hasten the onset of thermosolutal instability in the absence of rotation. In the presence of rotation, Hall currents postpone/hasten the onset of instability depending upon the value of wavenumbers. Again, the dispersion relation is analyzed numerically & the results depicted graphically. The stable solute gradient and magnetic field (and corresponding Hall currents) introduce oscillatory modes in the system which were non-existent in their absence. The case of overstability is discussed & sufficient conditions for non-existence of overstability are derived.     

Chemical composition and larvicidal activity of Zanthoxylum armatum against diamondback moth,Plutella xylostella

The diamondback moth, Plutella xylostella (L.) (Lepidoptera: Yponomeutidae) is the most serious pest of cruciferous crops grown in the world causing economic yield loss. Several synthetic insecticides have been used against P. xylostella but satisfactory control was not achieved due to development of resistance to insecticides. Therefore, the present study was carried out to screen different fractions of Zanthoxylum armatum for their insecticidal activities against second instar larvae of P. xylostella. Results indicate, all the fractions showed activity to P. xylostella. However, n-hexane fraction of Z. armatum showed maximum larvicidal activity with minimum LC₅₀ value of 2988.6 ppm followed by ethanol (LC₅₀ = 12779.7 ppm) and methanol fraction (LC₅₀ = 12908.8 ppm) whereas chloroform fraction was least toxic (LC₅₀ = 16750.6 ppm). The GC–MS analysis of n-hexane fraction of leaf extract showed maximum larvicidal activity, which may be due to two major compounds i.e. 2-undecanone (19.75%) and 2-tridecanone (11.76%).     

A High Pressure Operando Spectroscopy Examination of Bimetal Interactions in ‘Metal Efficient’ Palladium/In2O3/Al2O3 Catalysts for CO2 Hydrogenation

CO₂ hydrogenation to methanol has the potential to serve as a sustainable route to a wide variety of hydrocarbons, fuels and plastics in the quest for net zero. Synergistic Pd/In₂O₃ (Palldium on Indium Oxide) catalysts show high CO₂ conversion and methanol selectivity, enhancing methanol yield. The identity of the optimal active site for this reaction is unclear, either as a Pd−In alloy, proximate metals, or distinct sites. In this work, we demonstrate that metal-efficient Pd/In₂O₃ species dispersed on Al₂O₃ can match the performance of pure Pd/In₂O₃ systems. Further, we follow the evolution of both Pd and In sites, and surface species, under operando reaction conditions using X-ray Absorption Spectroscpy (XAS) and infrared (IR) spectroscopy. In doing so, we can determine both the nature of the active sites and the influence on the catalytic mechanism.