Virtual screening of selective inhibitors of phosphopantetheine adenylyltransferase from <Emphasis Type="Italic">Mycobacterium tuberculosis</Emphasis>

Bacterial phosphopantetheine adenylyltransferase from Mycobacterium tuberculosis (PPAT Mt) is a convenient target protein for the directed search for selective inhibitors as potent antituberculosis drugs. Four compounds suitable for the detailed investigation of their interactions with PPAT Mt were found by virtual screening. The active-site region of the enzyme was chosen as the ligand-binding site. The positions of the ligands found by the docking were refined by molecular dynamics simulation. The nearest environment of the ligands, the positions of which in the active site of the enzyme were found in a computational experiment, was analyzed. The compounds under consideration were shown to directly interact with functionally important active-site amino-acid residues and block access of substrates to the active site. Therefore, these compounds can be used for the design of selective inhibitors of PPAT Mt as potent antituberculosis drugs.     

Structure and thermoelastic martensitic transformations in ternary Ni–Ti–Hf alloys with a high-temperature shape memory effect

The effect of alloying by 12–20 at % Hf on the structure, the phase composition, and the thermoelastic martensitic transformations in ternary alloys of the quasi-binary NiTi–NiHf section is studied by transmission electron microscopy, scanning electron microscopy, electron diffraction, and X-ray diffraction. The electrical resistivity is measured at various temperatures to determine the critical transformation temperatures. The data on phase composition are used to plot a full diagram for the high-temperature thermoelastic B2 ? B19’ martensitic transformations, which occur in the temperature range 320–600 K when the hafnium content increases from 12 to 20 at %. The lattice parameters of the B2 and B19’ phases are measured, and the microstructure of the B19’ martensite is analyzed.     

Analytical estimation of dislocation distribution at the tip of arrested cracks

Computer simulation technique is used for studying the plastic flow at the tip of an arrested crack in lithium fluoride crystals. Two stages of the dislocation structure formation at the tip of a crack are analyzed: the formation of slip lines at the instant of crack arresting, and their evolution after sample unloading and partial healing of the crack. The size and the number of dislocations in a slip line are determined as functions of the loading force at the instant of crack arresting and on frictional stresses. It is shown that, during sample unloading and healing, some dislocations emerge at the plane of the crack under the action of mutual repulsion and image forces, so that the dislocation density attains its maximum value at a distance from the crack tip. A finite region free of dislocations exists in the immediate vicinity of the crack tip.     

Effect of gallium alloying on the structure,the phase composition,and the thermoelastic martensitic transformations in ternary Ni–Mn–Ga alloys

The effect of gallium alloying on the structure, the phase composition, and the properties of quasibinary Ni₅₀Mn_50–zGa_z (0 ? z ? 25 at %) alloys is studied over a wide temperature range. The influence of the alloy composition on the type of crystal structure in high-temperature austenite and martensite and the critical martensitic transformation temperatures is analyzed. A general phase diagram of the magnetic and structural transformations in the alloys is plotted. The temperature–concentration boundaries of the B2 and L2₁ superstructures in the austenite field, the tetragonal L1₀ (2M) martensite, and the 10M and 14M martensite phases with complex multilayer crystal lattices are found. The predominant morphology of martensite is shown to be determined by the hierarchy of the packets of thin coherent lamellae of nano- and submicrocrystalline crystals with planar habit plane boundaries close to {011}_B2. Martensite crystals are twinned along one of the 24 \(24\left\{ {011} \right\}{\left\langle {01\bar 1} \right\rangle _{B2}}\) “soft” twinning shear systems, which provides coherent accommodation of the martensitic transformation–induced elastic stresses.     

Effect of copper on the structure–phase transformations and the properties of quasi-binary TiNi–TiCu alloys

The effect of copper alloying up to 25 at % on the structure–phase transformations and the physicomechanical properties of ternary alloys from the quasi-binary TiNi–TiCu section is studied by measuring the physicomechanical properties, transmission electron microscopy, scanning electron microscopy, electron diffraction, and X-ray diffraction (XRD). The data of temperature measurements of the electrical resistivity and the magnetic susceptibility and XRD data are used to plot a general diagram for the thermoelastic B2 ? B19', B2 ? B19 ? B19', and B2 ? B19 martensitic transformations, which occur in the alloys upon cooling as the copper content increases in the ranges 0–8, 8–15, and 15–25 at % Cu, respectively. The experimental results are compared to the well-known data, including differential scanning calorimetry data, obtained for these alloys. The changes in the mechanical properties and the microstructure of the alloys in the state of B19 or B19' martensite are discussed.     

Synthesis of C-terminal fragments of bombesin and their analogues

With the aim of structural-functional studies in the bombesin series, a number of bombesin fragments and analogues have been synthesized. The synthesis was performed by the carbodiimide method and by the activated-ester method. Fragments with the sequences 7–14, 8–14, and 9–14 were obtained by 4+4, 3+4, and 2+4 schemes and a pentapeptide with the sequence 9–13 by a 3 + 2 scheme. Acetylation of the octapeptide BN(7–14) was carried out by the action of acetic anhydride in pyridine. Analogues of the C-terminal nonapeptide of bombesin [DPhe⁷]BN(6–14) and [Pro⁶, Gly⁷, DAla¹¹]BN(6–14) were synthesized by fragment condensation using the 5 + 4 scheme. The individuality of the compounds obtained was confirmed by their chromatographic behavior on plates coated with silica gel, and by the results of amino acid analysis, high-voltage electrophoresis, and high-performance liquid chromatography, and their structures were confirmed by the results of high-resolution¹H NMR spectroscopy (360 MHz). In experiments on rabbits, in a dose of 1 µg with central administration the full hypothermic effect of bombesin was shown by the preparation [AcGln⁷]BN(7–14), while the preparation [DPhe⁷]BN(6–14) and [Pro⁶,Gly⁷,DAla¹¹]BN(6–14) possessed only a slight effect (～1% of the activity of bombesin).     

On microcrack nucleation at twin vertices and boundaries in bcc and fcc metals

Nucleation of microcracks at the vertex and boundary of a decelerated twin is studied for a number of bcc and fcc metals. A twin and its boundary are represented as stepped pileups of twinning dislocations located in the neighboring glide planes. The formation of microcracks through the merging of head dislocations by the force and thermally-activated mechanisms is analyzed. Analytical expressions are obtained that describe the conditions necessary for microcrack nucleation at the vertices of stepped dislocation pileups. It is established that with an increase in the shear-modulus value, the critical parameters of microcrack nucleation by the two above mechanisms become closer in all the metals considered.     

Formation of nanostructured states in ternary TiNiFe-based shape memory alloys during megaplastic deformation and subsequent heat treatment

The ternary metastable TiNiFe alloys that exhibit a low-temperature shape memory effect and are subjected to plastic deformation by rolling or high-pressure torsion followed by heat treatment are studied by X-ray diffraction, transmission electron microscopy, scanning electron microscopy, and electrical resistivity measurements. It is found that moderate plastic deformation of a Ti₅₀Ni₄₉Fe₁ alloy at room temperature initiates the thermoelastic B2 ? B19’ martensitic transformation and the formation of a developed banded dislocation and twin substructure in the B19’ martensite. This deformation of a Ti₅₀Ni₄₇Fe₃ alloy forms a similar dislocation substructure but in B2 austenite. Megaplastic deformation by high-pressure torsion causes amorphization in the Ti₅₀Ni₄₉Fe₁ alloy and nanofragmentation in the Ti₅₀Ni₄₇Fe₃ alloy. The evolution of the nanostructure and the martensitic transformations in TiNiFe-based ternary alloys is studied during plastic deformation and subsequent annealing at various temperatures.